AcromegalyPhase 3NCT02354508
Pasireotide in Patients With Acromegaly Inadequately Controlled With First Generation Somatostatin Analogues
A Phase 3 study testing Pasireotide LAR in people with Acromegaly, run by Novartis Pharmaceuticals at 50 sites in 15 countries.
Trial summary
This is a phase IIIb multicenter, open-label; single arm study to evaluate the efficacy and safety of pasireotide LAR 40 mg and 60 mg in patients with inadequately controlled acromegaly with maximal approved doses of first generation somatostatin analogues. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acromegaly
- What is being tested?
- Pasireotide LAR
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 123 participants
- Where
- 50 sitesin 15 countries
- Study dates
- 31 Mar 2015to 27 Sep 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent
- Male and female patients ≥18 years
- Patients with confirmed diagnosis of inadequately controlled acromegaly (mean GH concentration ≥1 μg/L and sex- and age-adjusted IGF-1 >1.3 x ULN)
- Patients treated with octreotide LAR (30 mg or 40 mg) or lanreotide ATG (120 mg) monotherapy for at least 3 months prior to screening
Who cannot join
- Concomitant treatment with other medications reducing GH and or IGF-1, unless discontinued 3 months prior to screening
- Patients with compression of the optic chiasm requiring surgical intervention
- Diabetic patients with HbA1c >8% at screening
- Patients who are hypothyroid and not on adequate replacement therapy
- Patients with symptomatic cholelithiasis and acute or chronic pancreatitis
- Patients with clinically significant valvular disease
Show all 28Show fewer
- Patients with risk factors for torsade de pointes (TdP)
- Hypokalaemia, hypomagnesaemia, uncontrolled hypothyroidism, family history of long QT syndrome or concomitant medications with known risk of TdP
- Patients with congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, advanced heart block, history of acute MI less than one year prior to study entry or clinically significant impairment in cardiovascular function.
- Concomitant disease(s) that could prolong the QT interval such as autonomic neuropathy (caused by diabetes or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure
- Patients with liver disease or ALT/AST > 2.0 X ULN, serum bilirubin >2.0 X ULN - Presence of Hepatitis B surface antigen or Hepatitis C antibody test
- Patients with serum creatinine >2.0 X ULN
- Patients with WBC <3 X 109/L; Hb 90% < LLN; PLT <100 X 109/L
- Patients with active or suspected acute or chronic uncontrolled infection
- Patients who have undergone major surgery/surgical therapy within 4 weeks prior to screening
- Patients with active malignant disease within the last five years (with the exception of basal cell carcinoma or carcinoma in situ of the cervix)
- Patients with abnormal coagulation (PT and/or APTT elevated by 30% above normal limits) or patients receiving anticoagulants that affect PT (prothrombin time) or APTT (activated partial thromboplastin time)
- History of syncope or family history of idiopathic sudden death
- History of immunocompromise, including a positive HIV test result (ELISA and Western blot)
- Known hypersensitivity to somatostatin analogues or any other component of pasireotide LAR
- Patients who have a history of alcohol or drug abuse in the 6 month period prior to receiving pasireotide
- Patients who have given a blood donation (of 400 ml or more) within 2 months before receiving pasireotide
- Patients who have participated in any clinical investigation with an investigational drug within 1 month prior to dosing
- Patients with any current or prior medical condition interfering with the conduct of the study or the evaluation of the study results
- Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will be unable to complete the entire study.
- Sexually active males unless they use a condom during intercourse while taking drug and for 3 months following last dose of pasireotide
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and 3 months following the last dose of pasireotide.
Trial locations and contacts
50 sites in 15 countries.
50 sites in 15 countries
Italy9 sites
Novartis Investigative Site
Ancona, AN, 60126
Novartis Investigative Site
Genova, GE, 16132
Novartis Investigative Site
Milan, MI, 20122
Novartis Investigative Site
Milan, MI, 20162
Novartis Investigative Site
Naples, 80131
Novartis Investigative Site
Padova, PD, 35128
Novartis Investigative Site
Palermo, PA, 90127
Novartis Investigative Site
Pisa, PI, 56124
Novartis Investigative Site
Torino, TO, 10126
France8 sites
Novartis Investigative Site
Angers, 49933
Novartis Investigative Site
Besançon, 25030
Novartis Investigative Site
Bron, 69677
Novartis Investigative Site
Nîmes, 30029
Novartis Investigative Site
Reims, 51092
Novartis Investigative Site
Rouen, 76031
Novartis Investigative Site
Saint-Herblain, 44800
Novartis Investigative Site
Vandœuvre-lès-Nancy, 54511
Turkey (Türkiye)5 sites
Novartis Investigative Site
Ankara, 06560
Novartis Investigative Site
Istanbul, TUR, 34098
Novartis Investigative Site
Izmir, 35340
Novartis Investigative Site
Kocaeli, 41380
Novartis Investigative Site
Pendik / Istanbul, Turkey, 34899
Argentina3 sites
Novartis Investigative Site
CABA, Buenos Aires, C1180AAX
Novartis Investigative Site
CABA, Buenos Aires, C1428AQK
Novartis Investigative Site
Mar del Plata, Buenos Aires, B7602CBM
Belgium3 sites
Novartis Investigative Site
Brussels, 1200
Novartis Investigative Site
Edegem, 2650
Novartis Investigative Site
Leuven, 3000
China3 sites
Novartis Investigative Site
Beijing, Beijing Municipality, 100730
Novartis Investigative Site
Chengdu, Sichuan, 610041
Novartis Investigative Site
Guangzhou, Guangdong, 510080
Mexico3 sites
Novartis Investigative Site
Durango, 34270
Novartis Investigative Site
Guadalajara, Jalisco, 44130
Novartis Investigative Site
Mexico City, Mexico City, 02990
Portugal3 sites
Novartis Investigative Site
Lisbon, 1349 019
Novartis Investigative Site
Porto, 4099-001
Novartis Investigative Site
Porto, 4200-319
United Kingdom3 sites
Novartis Investigative Site
London, EC1A 7BE
Novartis Investigative Site
Nottingham, NG7 2UH
Novartis Investigative Site
Plymouth, PL6 8DH
Colombia2 sites
Novartis Investigative Site
Bogotá
Novartis Investigative Site
Floridablanca, Santander Department, 57-7
Hungary2 sites
Novartis Investigative Site
Budapest, 1085
Novartis Investigative Site
Szeged, HUN, 6720
Malaysia2 sites
Novartis Investigative Site
Pulau Pinang, 10990
Novartis Investigative Site
Wilayah Persekutuan, 62502
Romania2 sites
Novartis Investigative Site
Bucharest, 011863
Novartis Investigative Site
Iași, 700127
Brazil1 site
Novartis Investigative Site
Rio de Janeiro, Rio de Janeiro, 21941-590
About this study
Official title: A Phase IIIb Multicenter, Open-label, Single Arm Study to Evaluate the Efficacy and Safety of Pasireotide in Patients With Acromegaly Inadequately Controlled With First Generation Somatostatin Analogues
This is a phase IIIb multicenter, open-label; single arm study to evaluate the efficacy and safety of pasireotide LAR 40 mg and 60 mg in patients with inadequately controlled acromegaly with maximal approved doses of first generation somatostatin analogues. The study will enroll inadequately controlled patients by high doses (maximal approved) of first-generation somatostatin analogues given for at least 3 months. Patients will receive pasireotide LAR 40 mg or 60 mg during the 36 week core study phase. Patients who have completed all visits of core phase and have completed all the assessments at the core phase completion visit can move into the 32-week extension phase. Patients can continue with study treatment until pasireotide LAR is commercially available and reimbursed in their respective country or until the end of the extension phase whichever occurs first.
Read the detailed description
This is a phase IIIb multicenter, open-label; single arm study to evaluate the efficacy and safety of pasireotide LAR 40 mg and 60 mg in patients with inadequately controlled acromegaly with maximal doses of first generation somatostatin analogues. The study will enroll inadequately controlled patients by high doses of first-generation somatostatin analogues given for at least 3 months.
Patients will be categorized into two groups. Group 1 consists of patients treated with octreotide LAR 30 mg from countries where octreotide LAR 40mg is approved for the treatment of acromegaly at the time of screening. These patients will start a 3-months run-in phase to receive 40mg octreotide before being considered eligible to enter the core treatment phase. After 3 months of treatment have been completed, and prior to the fourth injection a mean GH and IGF-1 will be assessed. Patients who are achieving biochemical control will be considered a screen failure and they will not qualify for the core phase of the study. They will continue treatment with octreotide LAR 40 mg outside the frame of this study.
Group 2 consists of patients treated with octreotide LAR 30 mg from countries where octreotide 40mg is NOT yet approved at the time of screening. This group also includes patients already treated with octreotide LAR 40 mg or lanreotide ATG 120 mg. Patients should have been treated with the first generation SSAs for at least 3 months prior to screening. Eligible patients can directly enter the core treatment phase of the study. A run-in phase is not required for this patient population.
In the core treatment phase patients will start treatment with pasireotide LAR 40 mg every 4 weeks. At week 12, the mean GH value and IGF-1value will be assessed. Patients who have not achieved biochemical control by week 12 and do not have any tolerability issues with pasireotide LAR 40 mg will have the dose increased to 60 mg. Patients who have achieved biochemical control by week 12 will maintain a dose of pasireotide LAR 40 mg. A mean GH value and IGF-1 value will be assessed every 12 weeks until Visit 777. At weeks 16 and 28, the investigator will be able to adjust the dose based on the achievement of biochemical control and drug tolerability. If tolerability issues occur, the dose can be decreased in 20 mg. Once the tolerability issue resolves, the patients should return to the dose previously received. Patients will be treated for a total of 36 weeks during the core phase. During this period any concomitant medication for the treatment of acromegaly is prohibited. Patients are required to complete a core phase completion visit 4 weeks after the last dose of pasireotide LAR is administered. Patients who discontinue from the core phase are also required to complete the core phase completion visit 4 weeks after receiving the last pasireotide LAR dose.
Patients who have completed all visits of core phase and have completed all the assessments at the core phase completion visit (Visit 777) can move into the extension phase. The core phase completion visit performed at Visit 777, will also be the first visit (Visit 18) of the extension phase. At Visit 18, the patients will receive the same dose of pasireotide LAR that they received at week 32 (Visit 17). At week 40 (Visit 19), the investigator will decide the treatment regimen and the pasireotide LAR dose based on the achievement of biochemical control at Visit 777. Patients achieving biochemical control at the end of the core phase will continue pasireotide LAR monotherapy at the same dose of the core phase. Patients who are uncontrolled at the end of the core phase will continue pasireotide LAR 60 mg and they will be allowed to receive concomitant treatment with medications used to treat acromegaly based on the investigator's clinical judgment. GH and IGF-1 levels will be assessed every 12 weeks until week 72. At weeks 52 and 64, the investigator will be able to adjust the dose of pasireotide LAR and the regimen of the concomitant medication used to acromegaly based on the patients achievement of biochemical control and drug tolerability. Patients will be treated for a total of 32 weeks in the extension phase and receive the last dose of study treatment at week 68 (Visit 26). Patients are required to complete an extension phase completion visit (Visit 778) 4 weeks after the last dose of pasireotide LAR is administered. Patients who prematurely discontinue from the extension phase are also required to complete the extension phase completion visit (Visit 778) 4 weeks after receiving the last dose of pasireotide LAR.
After discontinuation from the study or completion of study treatment either at the core phase or extension phase of the study, all patients will be followed for safety for 12 weeks (84 days) after the last study drug administration. This visit can be performed by phone, a study visit for follow-up is not mandatory.
- Conditions
- Acromegaly
- Being tested
- Pasireotide LAR
- Keywords
- acromegaly, GH, IGF-1, pasireotide LAR, SOM230, first generation, somatostatin analogues, growth disorder, gigantism, Pituitary adenoma, pituitary gigantism
- Medical subject headings
- Acromegaly, Growth Disorders, Gigantism, Pituitary Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pasireotide LARDrug
Also called SOM230
Pasireotide 40 mg and 60 mg. Pasireotide 20 mg which was allowed for dose decrease in case of adverse event.
| Study group | Role | What they receive |
|---|---|---|
| Pasireotide LAR | Experimental | Patients who qualify for the core phase of the study will be treated with pasireotide LAR 40 mg initially. Patients not achieving biochemical control can be up-titrated to pasireotide LAR 60 mg. Receives: Drug: Pasireotide LAR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 by Previous Treatment and Overall
Percentage of participants who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36.
Measured: Week 36
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 for Participants Up-titrated to Pasireotide LAR 60 mg
Percentage of participants who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36, for participants who had been up-titrated with pasireotide LAR 60 mg.
Measured: Week 36
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36
Percentage of participants who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36.
Measured: Wek 36
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36
Percentage of patients who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36, by previous treatment, type of therapy and overall.
Measured: Week 36
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 Overall by Baseline Diabetic Status
Percentage of participants who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36, overall by baseline diabetic status.
Measured: Week 36
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 by Previous Treatment and Overall - LOCF
Percentage of participants who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36, by previous treatment and overall - last observation carried forward (LOCF)
Measured: Week 36
Secondary outcomes (18)
Core Phase: Change in Mean Growth Hormone (GH) Values From Baseline to Week 36
Core phase - Changes in mean GH from study baseline to week 36.
Measured: Baseline, week 36
Core Phase: Change in Standardized IGF-1 Values From Baseline to Week 36
Core phase - Changes in standardized IGF-1 from study baseline to week 36.
Measured: Baseline, week 36
Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN
Percentage of participants achieving GH <1 μg/L and IGF-1 <ULN at weeks 12 and 24 overall and by GH level at screening.
Measured: Week 12, Week 24, Week 36
Core Phase: Percentage of Participants With IGF-1 <ULN Overall by GH Level at Screening
Percentage of participants achieving IGF-1 <ULN at weeks 12, 24 \& 36.
Measured: Weeks 12, 24 & 36
Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN Overall by Baseline Diabetic Status
Core phase - Percentage of patients achieving GH <1μg/L at week 12, 24, 36 overall and by GH level at screening.
Measured: Weeks 12, 24 & 36
Core Phase: Change From Baseline in Scores as Measured by Acromegaly Quality of Life (AcroQoL)
Evaluation of effect of pasireotide LAR on Health Related Quality of Life (HRQoL) was assessed using AcroQoL, an acromegaly-specific quality of life instrument. The AcroQol instrument is comprised of 22 questions divided into two scales: one evaluating physical aspects (8 items) and the other that addresses psychological aspects (14 items). The psychological scale can also be further divided into subscale that evaluates physical appearance and the other subscale focused on the impact of the disease on personal relationships of the patient (7 items each). Each of the questions has a 5-item Likert scale. For each dimension the scores range from 0-4 with 0 being the lowest impact and 4 being the most severe.
Measured: Baseline, Weeks 12, 24 & 36
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms
Symptoms of acromegaly were collected at various visits. The measurement was to be provided on a scale of 1-15 including half sizes. Investigators asked the participants to score the following symptoms of acromegaly: headache, fatigue, perspiration, paresthesias, osteoarthralgia according to a five-point score scale (0=absent, 1=mild, 2=moderate, 3=severe, 4=very severe).
Measured: Weeks 12, 24 & 36
Core Phase: Percentage of Participants With Acromegaly Shift Symptoms From Baseline to Most Extreme Post-baseline
Symptoms of acromegaly were collected at various visits. The measurement was to be provided on a scale of 1-15 including half sizes. Investigators asked the participants to score the following symptoms of acromegaly: headache, fatigue, perspiration, paresthesias, osteoarthralgia according to a five-point score scale (0=absent, 1=mild, 2=moderate, 3=severe, 4=very severe).
Measured: Weeks 12, 24 & 36
Core Phase: Change From Baseline in EQ-5D-5L Index Scores
Evaluation of effect of pasireotide LAR on health status, measured by EQ-5D-5L, a valid and reliable instrument for measuring general health status. The EQ-5D-5L consists of 2 pages - the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The EQ VAS records the respondent's self-rated health on a 20-cm vertical, visual analogue scale with endpoints labeled 'the best health you can imagine' and 'the worst health you can imagine'. This scale is numbered from 0 to 100. 100 means the best health you can imagine.
0 means the worst health you can imagine.
Measured: Baseline, Weeks 12, 24 & 36
Core Phase: Change From Baseline in EQ-5D-5L VAS Assessment
Evaluation of effect of pasireotide LAR on health status, measured by EQ-5D-5L, a valid and reliable instrument for measuring general health status. The EQ-5D-5L consists of 2 pages - the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The EQ VAS records the respondent's self-rated health on a 20-cm vertical, visual analogue scale with endpoints labeled 'the best health you can imagine' and 'the worst health you can imagine'. This scale is numbered from 0 to 100. 100 means the best health you can imagine.
0 means the worst health you can imagine.
Measured: Baseline, Weeks 12, 24 & 36
Extension Phase: Percentage of Participants With Mean GH < 1 μg/L and IGF-1 < ULN at Weeks 48, 60 & 72 (Up-titrated to Pasireotide LAR 60 mg)
Percentage of patients achieving IGF-1 <ULN at weeks 48, 60 \& 72 for participants with up-titrated to Pasireotide LAR 60 mg mg
Measured: Weeks 48, 60 & 72
Extension Phase: Percentage of Participants With Mean GH < 1 μg/L and IGF-1 < ULN at Weeks 48, 60 and 72 (Overall by Baseline Diabetic Status)
Percentage of participants achieving IGF-1 <ULN at week 46, 60 and 72 overall by baseline diabetic status
Measured: Weeks 48, 60, 72
Extension Phase: Percentage of Participants With Mean GH < 1 μg/L at Weeks 48, 60, 72 and Overall, Pasireotide Montherapy and Pasireotide With Concomittant Medication and by GH Level at Screening
Percentage of patients achieving GH <1 μg/L and IGF-1 <ULN at week 48 by treatment with pasireotide LAR alone or with concomitant medications used to treat acromegaly
Measured: Weeks 48, 60, 72
Extension Phase: Change From Baseline in Scores as Measured by Acromegaly Quality of Life (AcroQoL)
Evaluation of effect of pasireotide LAR on Health Related Quality of Life (HRQoL) was assessed using AcroQoL, an acromegaly-specific quality of life instrument. The AcroQol instrument is comprised of 22 questions divided into two scales: one evaluating physical aspects (8 items) and the other that addresses psychological aspects (14 items). The psychological scale can also be further divided into subscale that evaluates physical appearance and the other subscale focused on the impact of the disease on personal relationships of the patient (7 items each). Each of the questions has a 5-item Likert scale. For each dimension the scores range from 0-4 with 0 being the lowest impact and 4 being the most severe.
Measured: Baseline, Weeks 48, 60 & 72
Extension Phase: Percentage of Participants Reporting Levels 1 - 5 by Dimensions of Acromegaly Symptoms
Symptoms of acromegaly were collected at various visits. The measurement was to be provided on a scale of 1-15 including half sizes. Investigators asked the participants to score the following symptoms of acromegaly: headache, fatigue, perspiration, paresthesias, osteoarthralgia according to a five-point score scale (0=absent, 1=mild, 2=moderate, 3=severe, 4=very severe).
Measured: Weeks 48, 60 & 72
Extension (Ext.) Phase: Percentage of Participants With Acromegaly Shift Symptoms From Extension Baseline to Most Extreme Post-extension Baseline
Symptoms of acromegaly were collected at various visits. The measurement was to be provided on a scale of 1-15 including half sizes. Investigators asked the participants to score the following symptoms of acromegaly: headache, fatigue, perspiration, paresthesias, osteoarthralgia according to a five-point score scale (0=absent, 1=mild, 2=moderate, 3=severe, 4=very severe).
Measured: Weeks 48, 60 & 72
Extension Phase: Change From Baseline in EQ-5D-5L Index Scores
Evaluation of effect of pasireotide LAR on health status, measured by EQ-5D-5L, a valid and reliable instrument for measuring general health status. The EQ-5D-5L consists of 2 pages - the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The EQ VAS records the respondent's self-rated health on a 20-cm vertical, visual analogue scale with endpoints labeled 'the best health you can imagine' and 'the worst health you can imagine'. This scale is numbered from 0 to 100. 100 means the best health you can imagine.
0 means the worst health you can imagine.
Measured: Baseline, Weeks 48, 60 & 72
Extension Phase: Change From Baseline in EQ-5D-5L VAS Assessment
Evaluation of effect of pasireotide LAR on health status, measured by EQ-5D-5L, a valid and reliable instrument for measuring general health status. The EQ-5D-5L consists of 2 pages - the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The EQ VAS records the respondent's self-rated health on a 20-cm vertical, visual analogue scale with endpoints labeled 'the best health you can imagine' and 'the worst health you can imagine'. This scale is numbered from 0 to 100. 100 means the best health you can imagine.
0 means the worst health you can imagine.
Measured: Baseline, Weeks 48, 60 & 72
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2015 (estimated)
- Study start31 Mar 2015
- Primary completion8 Jan 2018
- Study completion27 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AcromegalyStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02354508
- Sponsor's protocol ID
- CSOM230C2413
- Other IDs
- 2014-002630-31, 2014
- Status last verified
- Dec 2019
- First submitted
- 29 Jan 2015
- Last updated
- 10 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
Publications
Gadelha M, Bex M, Colao A, Pedroza Garcia EM, Poiana C, Jimenez-Sanchez M, Yener S, Mukherjee R, Bartalotta A, Maamari R, Raverot G. Evaluation of the Efficacy and Safety of Switching to Pasireotide in Patients With Acromegaly Inadequately Controlled With First-Generation Somatostatin Analogs. Front Endocrinol (Lausanne). 2020 Feb 3;10:931. doi: 10.3389/fendo.2019.00931. eCollection 2019.
PubMed 32117045
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIIb Multicenter, Open-label, Single Arm Study to Evaluate the Efficacy and Safety of Pasireotide in Patients With Acromegaly Inadequately Controlled With First Generation Somatostatin Analogues
- ClinicalTrials.gov ID
- NCT02354508
- Acronym / sponsor ID
- CSOM230C2413
- Conditions
- Acromegaly
- Keywords
- acromegaly, GH, IGF-1, pasireotide LAR, SOM230, first generation, somatostatin analogues, growth disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 123 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 31 Mar 2015 (actual)
- Primary completion
- 8 Jan 2018 (actual)
- Study completion
- 27 Sep 2018 (actual)
- First posted
- 3 Feb 2015 (estimated)
- Results
- Posted 4 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase IIIb multicenter, open-label; single arm study to evaluate the efficacy and safety of pasireotide LAR 40 mg and 60 mg in patients with inadequately controlled acromegaly with maximal approved doses of first generation somatostatin analogues. The study will enroll inadequately controlled patients by high doses (maximal approved) of first-generation somatostatin analogues given for at least 3 months. Patients will receive pasireotide LAR 40 mg or 60 mg during the 36 week core study phase. Patients who have completed all visits of core phase and have completed all the assessments at the core phase completion visit can move into the 32-week extension phase. Patients can continue with study treatment until pasireotide LAR is commercially available and reimbursed in their respective country or until the end of the extension phase whichever occurs first.
Detailed description
This is a phase IIIb multicenter, open-label; single arm study to evaluate the efficacy and safety of pasireotide LAR 40 mg and 60 mg in patients with inadequately controlled acromegaly with maximal doses of first generation somatostatin analogues. The study will enroll inadequately controlled patients by high doses of first-generation somatostatin analogues given for at least 3 months.
Patients will be categorized into two groups. Group 1 consists of patients treated with octreotide LAR 30 mg from countries where octreotide LAR 40mg is approved for the treatment of acromegaly at the time of screening. These patients will start a 3-months run-in phase to receive 40mg octreotide before being considered eligible to enter the core treatment phase. After 3 months of treatment have been completed, and prior to the fourth injection a mean GH and IGF-1 will be assessed. Patients who are achieving biochemical control will be considered a screen failure and they will not qualify for the core phase of the study. They will continue treatment with octreotide LAR 40 mg outside the frame of this study.
Group 2 consists of patients treated with octreotide LAR 30 mg from countries where octreotide 40mg is NOT yet approved at the time of screening. This group also includes patients already treated with octreotide LAR 40 mg or lanreotide ATG 120 mg. Patients should have been treated with the first generation SSAs for at least 3 months prior to screening. Eligible patients can directly enter the core treatment phase of the study. A run-in phase is not required for this patient population.
In the core treatment phase patients will start treatment with pasireotide LAR 40 mg every 4 weeks. At week 12, the mean GH value and IGF-1value will be assessed. Patients who have not achieved biochemical control by week 12 and do not have any tolerability issues with pasireotide LAR 40 mg will have the dose increased to 60 mg. Patients who have achieved biochemical control by week 12 will maintain a dose of pasireotide LAR 40 mg. A mean GH value and IGF-1 value will be assessed every 12 weeks until Visit 777. At weeks 16 and 28, the investigator will be able to adjust the dose based on the achievement of biochemical control and drug tolerability. If tolerability issues occur, the dose can be decreased in 20 mg. Once the tolerability issue resolves, the patients should return to the dose previously received. Patients will be treated for a total of 36 weeks during the core phase. During this period any concomitant medication for the treatment of acromegaly is prohibited. Patients are required to complete a core phase completion visit 4 weeks after the last dose of pasireotide LAR is administered. Patients who discontinue from the core phase are also required to complete the core phase completion visit 4 weeks after receiving the last pasireotide LAR dose.
Patients who have completed all visits of core phase and have completed all the assessments at the core phase completion visit (Visit 777) can move into the extension phase. The core phase completion visit performed at Visit 777, will also be the first visit (Visit 18) of the extension phase. At Visit 18, the patients will receive the same dose of pasireotide LAR that they received at week 32 (Visit 17). At week 40 (Visit 19), the investigator will decide the treatment regimen and the pasireotide LAR dose based on the achievement of biochemical control at Visit 777. Patients achieving biochemical control at the end of the core phase will continue pasireotide LAR monotherapy at the same dose of the core phase. Patients who are uncontrolled at the end of the core phase will continue pasireotide LAR 60 mg and they will be allowed to receive concomitant treatment with medications used to treat acromegaly based on the investigator's clinical judgment. GH and IGF-1 levels will be assessed every 12 weeks until week 72. At weeks 52 and 64, the investigator will be able to adjust the dose of pasireotide LAR and the regimen of the concomitant medication used to acromegaly based on the patients achievement of biochemical control and drug tolerability. Patients will be treated for a total of 32 weeks in the extension phase and receive the last dose of study treatment at week 68 (Visit 26). Patients are required to complete an extension phase completion visit (Visit 778) 4 weeks after the last dose of pasireotide LAR is administered. Patients who prematurely discontinue from the extension phase are also required to complete the extension phase completion visit (Visit 778) 4 weeks after receiving the last dose of pasireotide LAR.
After discontinuation from the study or completion of study treatment either at the core phase or extension phase of the study, all patients will be followed for safety for 12 weeks (84 days) after the last study drug administration. This visit can be performed by phone, a study visit for follow-up is not mandatory.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pasireotide LAR | Experimental | Drug: Pasireotide LARPatients who qualify for the core phase of the study will be treated with pasireotide LAR 40 mg initially. Patients not achieving biochemical control can be up-titrated to pasireotide LAR 60 mg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Written informed consent
- Male and female patients ≥18 years
- Patients with confirmed diagnosis of inadequately controlled acromegaly (mean GH concentration ≥1 μg/L and sex- and age-adjusted IGF-1 >1.3 x ULN)
- Patients treated with octreotide LAR (30 mg or 40 mg) or lanreotide ATG (120 mg) monotherapy for at least 3 months prior to screening
Key exclusion criteria (28 listed)
- Concomitant treatment with other medications reducing GH and or IGF-1, unless discontinued 3 months prior to screening
- Patients with compression of the optic chiasm requiring surgical intervention
- Diabetic patients with HbA1c >8% at screening
- Patients who are hypothyroid and not on adequate replacement therapy
- Patients with symptomatic cholelithiasis and acute or chronic pancreatitis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pasireotide LARAlso: SOM230Pasireotide 40 mg and 60 mg. Pasireotide 20 mg which was allowed for dose decrease in case of adverse event. | Drug | Pasireotide LAR |
Primary outcome
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 by Previous Treatment and Overall
Time frame: Week 36
Percentage of participants who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36.
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 for Participants Up-titrated to Pasireotide LAR 60 mg
Time frame: Week 36
Percentage of participants who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36, for participants who had been up-titrated with pasireotide LAR 60 mg.
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36
Time frame: Wek 36
Percentage of participants who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36.
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36
Time frame: Week 36
Percentage of patients who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36, by previous treatment, type of therapy and overall.
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 Overall by Baseline Diabetic Status
Time frame: Week 36
Percentage of participants who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36, overall by baseline diabetic status.
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 by Previous Treatment and Overall - LOCF
Time frame: Week 36
Percentage of participants who achieved biochemical control defined as GH <1μg/L and IGF-1 <ULN at week 36, by previous treatment and overall - last observation carried forward (LOCF)
18 secondary outcomes
Core Phase: Change in Mean Growth Hormone (GH) Values From Baseline to Week 36
Time frame: Baseline, week 36
Core Phase: Change in Standardized IGF-1 Values From Baseline to Week 36
Time frame: Baseline, week 36
Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN
Time frame: Week 12, Week 24, Week 36
Core Phase: Percentage of Participants With IGF-1 <ULN Overall by GH Level at Screening
Time frame: Weeks 12, 24 & 36
Core Phase: Percentage of Participants With Mean GH <1 μg/L and IGF-1 <ULN Overall by Baseline Diabetic Status
Time frame: Weeks 12, 24 & 36
Core Phase: Change From Baseline in Scores as Measured by Acromegaly Quality of Life (AcroQoL)
Time frame: Baseline, Weeks 12, 24 & 36
Core Phase: Percentage of Participants Reporting Levels 0 - 4 by Dimensions of Acromegaly Symptoms
Time frame: Weeks 12, 24 & 36
Core Phase: Percentage of Participants With Acromegaly Shift Symptoms From Baseline to Most Extreme Post-baseline
Time frame: Weeks 12, 24 & 36
Core Phase: Change From Baseline in EQ-5D-5L Index Scores
Time frame: Baseline, Weeks 12, 24 & 36
Core Phase: Change From Baseline in EQ-5D-5L VAS Assessment
Time frame: Baseline, Weeks 12, 24 & 36
Extension Phase: Percentage of Participants With Mean GH < 1 μg/L and IGF-1 < ULN at Weeks 48, 60 & 72 (Up-titrated to Pasireotide LAR 60 mg)
Time frame: Weeks 48, 60 & 72
Extension Phase: Percentage of Participants With Mean GH < 1 μg/L and IGF-1 < ULN at Weeks 48, 60 and 72 (Overall by Baseline Diabetic Status)
Time frame: Weeks 48, 60, 72
Extension Phase: Percentage of Participants With Mean GH < 1 μg/L at Weeks 48, 60, 72 and Overall, Pasireotide Montherapy and Pasireotide With Concomittant Medication and by GH Level at Screening
Time frame: Weeks 48, 60, 72
Extension Phase: Change From Baseline in Scores as Measured by Acromegaly Quality of Life (AcroQoL)
Time frame: Baseline, Weeks 48, 60 & 72
Extension Phase: Percentage of Participants Reporting Levels 1 - 5 by Dimensions of Acromegaly Symptoms
Time frame: Weeks 48, 60 & 72
Extension (Ext.) Phase: Percentage of Participants With Acromegaly Shift Symptoms From Extension Baseline to Most Extreme Post-extension Baseline
Time frame: Weeks 48, 60 & 72
Extension Phase: Change From Baseline in EQ-5D-5L Index Scores
Time frame: Baseline, Weeks 48, 60 & 72
Extension Phase: Change From Baseline in EQ-5D-5L VAS Assessment
Time frame: Baseline, Weeks 48, 60 & 72
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32117045Gadelha M, Bex M, Colao A, Pedroza Garcia EM, Poiana C, Jimenez-Sanchez M, Yener S, Mukherjee R, Bartalotta A, Maamari R, Raverot G. Evaluation of the Efficacy and Safety of Switching to Pasireotide in Patients With Acromegaly Inadequately Controlled With First-Generation Somatostatin Analogs. Front Endocrinol (Lausanne). 2020 Feb 3;10:931. doi: 10.3389/fendo.2019.00931. eCollection 2019.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
50 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pasireotide LAR in people with Acromegaly, run by Novartis Pharmaceuticals at 50 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in Italy, France, Turkey (Türkiye), Argentina, Belgium and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Core Phase: Percentage of Participants With Mean GH < 1 g/L and IGF-1 < ULN at Week 36 by Previous Treatment and Overall (time frame: Week 36). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02354508, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2019.