Solid TumoursPhase 1NCT04179071
A Study in Healthy Male Subjects to Understand How Savolitinib Behaves Inside the Body (Pharmacokinetics) When Administered Alone and in Combination With Famotidine
A Phase 1 study testing Savolitinib and Famotidine in people with Solid Tumours, run by AstraZeneca at 1 site in United States.
Trial summary
This will be an open-label, randomised, 2 part (Part A and Part B), 2 treatment (savolitinib alone or in combination with famotidine), crossover study in healthy, non Japanese, male subjects, performed at a single study centre. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Solid Tumours
- What is being tested?
- Savolitinib and Famotidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Dec 2019to 11 Mar 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Provision of signed and dated written informed consent prior to any study specific procedures.
- Healthy, non-Japanese male subjects with suitable veins for cannulation or repeated venipuncture: male subjects aged 18 to 65 years (inclusive).
- Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive; and weigh at least 50 kg and no more than 100 kg inclusive.
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBL) less than or equal to the upper limit of normal for the institution.
- Have a calculated creatinine clearance greater than 80 mL/min using the Cockcroft-Gault formula at screening.
- Provision of signed, written and dated informed consent for optional genetic/biomarker research. If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this protocol.
Who cannot join
- Subject that has at least 1 parent or grandparent (maternal or paternal) of Japanese ethnicity.
- Subjects who screen positive for Helicobacter pylori bacteria.
- History of any clinically significant disease or disorder which, in the opinion of the Principal Investigator (PI), may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.
- History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of either study drug (savolitinib or famotidine).
- Planned in-patient surgery, dental procedure, or hospitalisation during the study.
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- Any clinically important abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the PI.
- Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
- Abnormal vital signs, after 5 minutes supine rest, defined as any of the following:
- Systolic BP <90 mmHg or ≥140 mmHg
- Diastolic BP <50 mmHg or ≥90 mmHg
- Heart rate <45 or >85 beats per minute.
- Any clinically important abnormalities in rhythm, conduction or morphology of the 12 lead resting electrocardiogram (ECG) that may interfere with the interpretation of QTc interval changes. These include healthy subjects with any of the following:
- Abnormal ST-T-wave morphology, particularly in the protocol-defined primary lead (V2) or left ventricular hypertrophy.
- PR interval shortening <120 ms (PR >110 ms but <120 ms is acceptable if there is no evidence of ventricular pre-excitation).
- PR interval prolongation (>200 ms). Intermittent second (Type 1 second degree block [Wenckebach Phenomenon] while asleep is not exclusive]) or third degree atrioventricular (AV) block, or AV dissociation.
- Persistent or intermittent complete bundle branch block, incomplete bundle branch block, or intraventricular conduction delay with QRS >110 ms. Subjects with QRS >110 ms but <115 ms are acceptable if there is no evidence of eg, ventricular hypertrophy or pre-excitation.
- Mean resting prolonged QTcF >450 ms or shortened QTcF <340 ms obtained from 3 ECGs.
- A history of additional risk factors for torsades de pointes (TdP) (eg, heart failure, chronic hypokalaemia not correctable with supplements, congenital or familial long QT syndrome, or family history of unexplained sudden death under 40 years of age in first-degree relatives).
- Use of any medications known to prolong the QT/QTc interval and cause TdP.
- Use of any prescribed or non prescribed medication including antacids, analgesics (other than ibuprofen up to 72 hours before dosing day), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of either study drug or longer if the medication has a long half life.
- Known or suspected history of drug abuse, as judged by the PI.
- Current smokers or those who have smoked or used nicotine products within the previous 30 days.
- History of alcohol abuse or excessive intake of alcohol as judged by the PI.
- Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate) as judged by the PI.
- Use of drugs with enzyme inducing properties such as St John's Wort, within 3 weeks prior to the first administration of either study drug.
- Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first admission on Day -1.
- Positive screen for drugs of abuse or cotinine (nicotine) or alcohol at screening and before each admission to the Study Centre.
- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the PI, or history of hypersensitivity to drugs with a similar chemical structure or class to savolitinib or famotidine.
- Plasma donation within 1 month of screening or any blood donation or loss of >500 mL during the 3 months prior to screening.
- Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of either study drug in this study. The period of exclusion begins 3 months after the final dose or one month after the last visit whichever is the longest. Note: subjects consented and screened, but not randomised in this study or a previous Phase I study, are not excluded.
- Subjects who have previously received savolitinib.
- Involvement of any AstraZeneca, Parexel, or study site employee or their close relatives.
- Judgment by the PI that the subject should not participate in the study if they have any ongoing or recent (ie, during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions, and requirements.
- Subjects who are vegans or vegetarians, or have medical dietary restrictions.
- Subjects who cannot communicate reliably with the PI.
- Vulnerable subjects, eg, kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
- In addition, any of the following is regarded as a criterion for exclusion from the genetic research:
- In addition, the following are considered criteria for exclusion from the optional genetic component of the study:
- Previous bone marrow transplant.
- Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection or previous bone marrow transplant.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-Label, Randomised, Two Part, Two Treatment Crossover Study in Healthy Subjects to Assess the Pharmacokinetics of Savolitinib When Administered Alone and in Combination With Famotidine
This will be an open-label, randomised, 2 part (Part A and Part B), 2 treatment (savolitinib alone or in combination with famotidine), crossover study in healthy, non Japanese, male subjects, performed at a single study centre.
Read the detailed description
Parts A and B will each have 2 Periods (Period 1 and Period 2) with a crossover design. Part B will be conducted only if results of Part A suggest a clinically meaningful effect of famotidine on savolitinib pharmacokinetics (PK) parameters. In both parts subjects will be randomly assigned 1:1 to receive one of the 2 treatment sequences: savolitinib alone first followed by crossover to the combination treatment of savolitinib+famotidine, or the reverse sequence. Subjects will be admitted for 4 days from one day before the first dose of the study drug and discharged 2 days after. There will be a washout period (no study treatment) of 14 days between the 2 Periods. The essential difference between the 2 parts is that in the combination treatment, famotidine will be administered 2 hours before savolitinib in Part A and 6 hours before savolitinib in Part B. A given subject will receive a total of 1 dose of famotidine and 2 doses of savolitinib during the study.
In this 2 part study, 16 subjects will be randomised in each part to ensure at least 14 evaluable subjects at the end of the last study period. If Part B is conducted, a total of 32 subjects overall are planned to be enrolled in the study. Additional subjects may be enrolled to ensure 14 evaluable subjects in each part if more than 2 subjects are deemed non evaluable.
- Conditions
- Solid Tumours
- Being tested
- Savolitinib, Famotidine
- Keywords
- Famotidine, Drug-drug interaction study, Small molecule kinase inhibitor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SavolitinibDrug
Subject will receive savolitinib tablet 600mg orally after a high-fat, high-calorie meal.
FamotidineDrug
Subjects will receive famotidine tablet 40mg orally after an overnight (minimum 8hours) of fasting.
| Study group | Role | What they receive |
|---|---|---|
| Savolitinib | Experimental | Subjects will receive single dose of 600mg savolitinib after a high-fat, high-calorie meal. Receives: Drug: Savolitinib |
| Savolitinib + Famotidine | Experimental | Subjects will receive savolitinib 600mg single dose after high-fat, high-calorie meal and after 1.5 hours (Part A) or 5.5 hours (Part B) of famotidine 40mg dose. Famotidine will be administered after an overnight fast of at least 8 hours with approximately 240 mL of water. Receives: Drug: Savolitinib; Drug: Famotidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum observed plasma concentration (Cmax) ratio
Cmax ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone) to assess effect of the gastric acid modifier, famotidine, on the PK of savolitinib.
Measured: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Area under plasma concentration-time curve from zero to infinity (AUC) ratio
AUC ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone) to assess effect of the gastric acid modifier, famotidine, on the PK of savolitinib.
Measured: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Secondary outcomes (12)
Number of subjects with having adverse events and/or abnormal findings in vital signs and/or laboratory evaluation and/or physical examination
To investigate the safety and tolerability of savolitinib in combination with famotidine.
Measured: From 28-day screening period to follow-up period i.e. 60 days
AUC geometric means ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone)
To assess the effect of famotidine on the PK of savolitinib metabolites M2 and M3 and to describe the PK parameters and the PK concentration-time profiles for savolitinib, M2, and M3 when savolitinib is administered alone and in combination with famotidine.
Measured: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Area under the plasma concentration curve from time zero to time of last quantifiable concentration AUC(0-t)
AUC(0-t) geometric means ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone) to assess the effect of famotidine on the PK of savolitinib metabolites M2 and M3 and to describe the PK parameters and the PK concentration-time profiles for savolitinib, M2, and M3 when savolitinib is administered alone and in combination with famotidine.
Measured: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Cmax geometric means ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone)
To assess the effect of famotidine on the PK of savolitinib metabolites M2 and M3 and to describe the PK parameters and the PK concentration-time profiles for savolitinib, M2, and M3 when savolitinib is administered alone and in combination with famotidine.
Measured: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Cmax metabolite-to-parent ratios (MRCmax)
MRCmax ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone) to assess the effect of famotidine on the PK of savolitinib metabolites M2 and M3 and to describe the PK parameters and the PK concentration-time profiles for savolitinib, M2, and M3 when savolitinib is administered alone and in combination with famotidine.
Measured: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
AUC metabolite-to-parent ratios (MRAUC)
MRAUC ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone) to assess the effect of famotidine on the PK of savolitinib metabolites M2 and M3 and to describe the PK parameters and the PK concentration-time profiles for savolitinib, M2, and M3 when savolitinib is administered alone and in combination with famotidine.
Measured: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
AUC(0-t) metabolite-to-parent ratios [MRAUC(0-t)]
MRAUC(0-t) ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone) to assess the effect of famotidine on the PK of savolitinib metabolites M2 and M3 and to describe the PK parameters and the PK concentration-time profiles for savolitinib, M2, and M3 when savolitinib is administered alone and in combination with famotidine.
Measured: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Time to reach maximum observed plasma concentration (tmax)
tmax ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone) to assess the effect of famotidine on the PK of savolitinib metabolites M2 and M3 and to describe the PK parameters and the PK concentration-time profiles for savolitinib, M2, and M3 when savolitinib is administered alone and in combination with famotidine.
Measured: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Half-life associated with terminal slope (λz) of a semi logarithmic concentration-time curve (t½,λz)
t½,λz ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone) to assess the effect of famotidine on the PK of savolitinib metabolites M2 and M3 and to describe the PK parameters and the PK concentration-time profiles for savolitinib, M2, and M3 when savolitinib is administered alone and in combination with famotidine.
Measured: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Terminal elimination rate constant (λz)
λz ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone) to assess the effect of famotidine on the PK of savolitinib metabolites M2 and M3 and to describe the PK parameters and the PK concentration-time profiles for savolitinib, M2, and M3 when savolitinib is administered alone and in combination with famotidine.
Measured: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)
Vz/F ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone) to assess the effect of famotidine on the PK of savolitinib metabolites M2 and M3 and to describe the PK parameters and the PK concentration-time profiles for savolitinib, M2, and M3 when savolitinib is administered alone and in combination with famotidine.
Measured: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
CL/F ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone) to assess the effect of famotidine on the PK of savolitinib metabolites M2 and M3 and to describe the PK parameters and the PK concentration-time profiles for savolitinib, M2, and M3 when savolitinib is administered alone and in combination with famotidine.
Measured: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2019
- Study start13 Dec 2019
- Primary completion11 Mar 2020
- Study completion11 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumoursStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- Dr. Ronald Goldwater, MD, Principal investigator, Parexel Early Phase Clinical Unit Baltimore (Study Centre)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04179071
- Sponsor's protocol ID
- D5084C00005
- Status last verified
- Jun 2020
- First submitted
- 25 Nov 2019
- Last updated
- 7 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Randomised, Two Part, Two Treatment Crossover Study in Healthy Subjects to Assess the Pharmacokinetics of Savolitinib When Administered Alone and in Combination With Famotidine
- ClinicalTrials.gov ID
- NCT04179071
- Acronym / sponsor ID
- D5084C00005
- Conditions
- Solid Tumours
- Keywords
- Famotidine, Drug-drug interaction study, Small molecule kinase inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 13 Dec 2019 (actual)
- Primary completion
- 11 Mar 2020 (actual)
- Study completion
- 11 Mar 2020 (actual)
- First posted
- 26 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This will be an open-label, randomised, 2 part (Part A and Part B), 2 treatment (savolitinib alone or in combination with famotidine), crossover study in healthy, non Japanese, male subjects, performed at a single study centre.
Detailed description
Parts A and B will each have 2 Periods (Period 1 and Period 2) with a crossover design. Part B will be conducted only if results of Part A suggest a clinically meaningful effect of famotidine on savolitinib pharmacokinetics (PK) parameters. In both parts subjects will be randomly assigned 1:1 to receive one of the 2 treatment sequences: savolitinib alone first followed by crossover to the combination treatment of savolitinib+famotidine, or the reverse sequence. Subjects will be admitted for 4 days from one day before the first dose of the study drug and discharged 2 days after. There will be a washout period (no study treatment) of 14 days between the 2 Periods. The essential difference between the 2 parts is that in the combination treatment, famotidine will be administered 2 hours before savolitinib in Part A and 6 hours before savolitinib in Part B. A given subject will receive a total of 1 dose of famotidine and 2 doses of savolitinib during the study.
In this 2 part study, 16 subjects will be randomised in each part to ensure at least 14 evaluable subjects at the end of the last study period. If Part B is conducted, a total of 32 subjects overall are planned to be enrolled in the study. Additional subjects may be enrolled to ensure 14 evaluable subjects in each part if more than 2 subjects are deemed non evaluable.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Savolitinib | Experimental | Drug: SavolitinibSubjects will receive single dose of 600mg savolitinib after a high-fat, high-calorie meal. |
| Savolitinib + Famotidine | Experimental | Drug: Savolitinib, Drug: FamotidineSubjects will receive savolitinib 600mg single dose after high-fat, high-calorie meal and after 1.5 hours (Part A) or 5.5 hours (Part B) of famotidine 40mg dose. Famotidine will be administered after an overnight fast of at least 8 hours with approximately 240 mL of water. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Provision of signed and dated written informed consent prior to any study specific procedures.
- Healthy, non-Japanese male subjects with suitable veins for cannulation or repeated venipuncture: male subjects aged 18 to 65 years (inclusive).
- Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive; and weigh at least 50 kg and no more than 100 kg inclusive.
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBL) less than or equal to the upper limit of normal for the institution.
- Have a calculated creatinine clearance greater than 80 mL/min using the Cockcroft-Gault formula at screening.
Key exclusion criteria (41 listed)
- Subject that has at least 1 parent or grandparent (maternal or paternal) of Japanese ethnicity.
- Subjects who screen positive for Helicobacter pylori bacteria.
- History of any clinically significant disease or disorder which, in the opinion of the Principal Investigator (PI), may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.
- History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of either study drug (savolitinib or famotidine).
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 |
|---|---|---|
| SavolitinibSubject will receive savolitinib tablet 600mg orally after a high-fat, high-calorie meal. | Drug | Savolitinib, Savolitinib + Famotidine |
| FamotidineSubjects will receive famotidine tablet 40mg orally after an overnight (minimum 8hours) of fasting. | Drug | Savolitinib + Famotidine |
Primary outcome
Maximum observed plasma concentration (Cmax) ratio
Time frame: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Cmax ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone) to assess effect of the gastric acid modifier, famotidine, on the PK of savolitinib.
Area under plasma concentration-time curve from zero to infinity (AUC) ratio
Time frame: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
AUC ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone) to assess effect of the gastric acid modifier, famotidine, on the PK of savolitinib.
12 secondary outcomes
Number of subjects with having adverse events and/or abnormal findings in vital signs and/or laboratory evaluation and/or physical examination
Time frame: From 28-day screening period to follow-up period i.e. 60 days
AUC geometric means ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone)
Time frame: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Area under the plasma concentration curve from time zero to time of last quantifiable concentration AUC(0-t)
Time frame: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Cmax geometric means ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone)
Time frame: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Cmax metabolite-to-parent ratios (MRCmax)
Time frame: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
AUC metabolite-to-parent ratios (MRAUC)
Time frame: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
AUC(0-t) metabolite-to-parent ratios [MRAUC(0-t)]
Time frame: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Time to reach maximum observed plasma concentration (tmax)
Time frame: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Half-life associated with terminal slope (λz) of a semi logarithmic concentration-time curve (t½,λz)
Time frame: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Terminal elimination rate constant (λz)
Time frame: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)
Time frame: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
Time frame: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2020.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm
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.
Dr. Ronald Goldwater, MD principal investigator
Parexel Early Phase Clinical Unit Baltimore (Study Centre)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Savolitinib and Famotidine in people with Solid Tumours, run by AstraZeneca at 1 site in United States.
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 6 inclusion and 41 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 7 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum observed plasma concentration (Cmax) ratio (time frame: At pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, and 48 hours post-dose on Day 1-3 and Day 16-18). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Jul 2020.