Parkinson's DiseasePhase 2NCT03187301
A Cardiac Safety Study of an Investigational Drug to See How if Affects the Heart in People With Parkinson's Disease Complicated by Motor Fluctuations "OFF" Episodes
A Phase 2 study testing APL-130277 and Moxifloxacin in people with Parkinson's Disease and Off Episodes of Parkinson Disease, run by Sumitomo Pharma America, Inc. at 15 sites in 2 countries.
Trial summary
A cardiac safety study of an investigational drug to see how it affects the heart in people with Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Parkinson's Disease, Off Episodes of Parkinson Disease
- What is being tested?
- APL-130277 and Moxifloxacin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 15 sitesin 2 countries
- Study dates
- 3 Aug 2017to 21 Dec 2017
- Phase
- Phase 2
- 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
- 1) Male or female ≥ 18 years of age. 2) Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank Criteria (excluding the "more than one affected relative" criterion).
- 3) Clinically meaningful response to Levodopa (L-Dopa). Subjects with or without well defined "OFF" episodes, as determined by the Investigator will be allowed.
- 4) Receiving stable doses of L-Dopa/carbidopa (immediate or sustained release) administered at least 3 times per day OR Rytary™ administered 3 times per day, for at least 4 weeks before the initial Screening Visit (SV1). Subjects receiving L-Dopa/carbidopa 3 times a day must also be on stable treatment with adjunctive PD medication regimens. These regimens bust me maintained at a stable dose for at least 4 weeks prior to the initial Screening Visit (SV1) with the exception that MAO-B inhibitors must be maintained at a stable level for at least 8 weeks prior to the initial Screening Visit (SV1).
- 5) No planned medication change(s) or surgical intervention anticipated during the course of study.
- 6) the subject must be able to have a drug withdrawal induced "OFF" episode.
- 7) Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.
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- 8) Mini-Mental State Examination (MMSE) score > 21.
- 9) If female and of childbearing potential, must agree to use one of the following methods of birth control throughout the study and until at least 30 days after final drug administration:
- Oral contraceptive
- Contraceptive patch
- Barrier (diaphragm, sponge or condom) plus spermicidal preparations
- Intrauterine contraceptive system
- Levonorgestrel implant
- Medroxyprogesterone acetate contraceptive injection
- Complete abstinence from sexual intercourse;
- Hormonal vaginal contraceptive ring; or
- Surgical sterilization or partner sterile (must have documented proof).
- 10)Male subjects must be either surgically sterile, agree to be sexually abstinent or use a barrier method of birth control (e.g., condom) from first study drug administration until at least 30 days after final drug administration
- 11)Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures to complete the study.
- 12)Able to understand the consent form, and to provide written informed consent.
- 13)Must be approved as a satisfactory candidate by the Enrollment Authorization Committee (EAC) and the Sponsor.
Who cannot join
- Atypical or secondary parkinsonism
- Nausea associated with the use of dopamine agonists that requires treatment with an antiemetic.
- Previous treatment with any of the following: a neurosurgical procedure for PD; continuous subcutaneous (s.c.) apomorphine infusion; or Duodopa/Duopa.
- Treatment with any form of s.c. apomorphine within 7 days prior to the initial Screening Visit (SV1). Subjects that stopped s.c. apomorphine for any reason other than systemic safety concerns or lack of efficacy may be considered.
- Contraindications to moxifloxacin or APOKYN®, or hypersensitivity to apomorphine hydrochloride or any macrolide antibiotic or any of the ingredients of APOKYN® (notably sodium metabisulfite).
- Female who is pregnant or lactating.
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- Participation in a clinical trial within 30 days prior to the initial Screening Visit (SV1), with the exception of clinical studies related to APL-13077.
- Receipt of any investigational (i.e., unapproved) medication within 30 days prior to the initial Screening Visit (SV1), with the exception of APL-13077.
- Any selective 5HT3 antagonists (i.e., ondansetron, granisetron, dolasetron, palonosetron, alosetron), dopamine antagonists (including Tigan [trimethobenzamide] and domperidone, but excluding quetiapine or clozapine) or dopamine depleting agents within 30 days prior to initial Screening Visit (SV1).
- Drug or alcohol dependency in the past 12 months.
- Subject has a history of malignancy within 5 years prior to SV1, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. Pituitary tumors of any duration are excluded.
- Documented abnormalities with ECGs including, arrhythmias, clinically meaningful interval irregularities, structural heart abnormalities ,myocardial infarction, presence or history of a pacemaker, or any abnormality of the ECG that in the opinion of the Investigator, would interfere with the ability to measure the QT interval, or correct the QT interval for heart rate.
- Male subjects with a screening corrected QT interval using Fridericia's formula (QTcF) of ≥ 450 ms; female subjects with a screening QT interval ≥ 470 ms. Eligibility will be based on the core laboratory ECG interpretation report.
- HR at screening < 45 bpm or > 100 bpm.
- QRS duration at screening >120 ms
- PR interval at screening >200 ms.
- Subjects with a history of cataplexy, unexplained syncope or seizures.
- Family history of sudden cardiac death.
- Heart failure (NYHA Class II or greater) and/or a myocardial infarction.
- Current use of any concomitant mediations that prolong the QT/QTc interval. Refer to https://crediblemeds.org for listing.
- History of additional risk factors for TdP (i.e., heart failure, hypokalemia, family history of Long QT Syndrome).
- Clinically significant medical, surgical, or laboratory abnormality in the opinion of the Investigator.
- Subject has a positive screening laboratory test result for human immunodeficiency virus (HIV).
- Subject has a positive screening laboratory test result for hepatitis B surface antigen or hepatitis C antibodies and has liver function test results at screening above the ULN for the reference laboratory.
- Major psychiatric disorder including, but not limited to, dementia, bipolar disorder, psychosis (including Parkinson's disease psychosis), or any disorder that, in the opinion of the Investigator, requires ongoing treatment that would make study participation unsafe or make treatment compliance difficult.
- History of clinically significant impulse control disorder(s).
- Dementia that precludes providing informed consent or would interfere with participation in the study.
- Current suicidal ideation within one year prior to the second Screening Visit (SV2) as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) or attempted suicide within the last 5 years.
- Donation of blood plasma in the 30 days prior to first dosing.
Trial locations and contacts
15 sites in 2 countries.
15 sites in 2 countries
United States10 sites
Atlanta Center for Medical Research
Atlanta, Georgia, 30331
The NeuroMedical Center, PC
Baton Rouge, Louisiana, 70810
Parkinson's Disease and Movement Disorders Center of Boca Raton
Boca Raton, Florida, 33486
QUEST Research Institute
Farmington Hills, Michigan, 48334
The Parkinson's and Movement Disorder Institute
Fountain Valley, California, 92708
MD Clinical
Hallandale, Florida, 33009
Clinical Trials, Inc.
Little Rock, Arkansas, 72205
Bioclinica Reserach
Orlando, Florida, 32806
Central Texas Neurology Consultants
Round Rock, Texas, 78681
Movement Disorders Center of Arizona
Scottsdale, Arizona, 85258
Italy5 sites
Casa di Cura villa Margherita (Neurologia)
Arcugnano, 36057
Centro Ricerche San Raffaele
Cassino, 03043
Agine Research Center, University Foundahon Chica-Pescara, Behavioral Neurology and Movement Disorders Unit
Chieti
Neurologia, Policlinico Tor Vergata
Rome, 00133
IRCCS San Raffaele Pisana,Clinical Trial Center
Rome, 00163
About this study
Official title: A Phase 2, Randomized, Double-Blind, Placebo Controlled, 3-Period Crossover, Positive Control, QT-Evaluation Study of APL-130277 in Subjects With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes)
A cardiac safety study of an investigational drug to see how it affects the heart in people with Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes)
Read the detailed description
This multi-center, Phase 2, Randomized, Double-Blind, Placebo Controlled, 3-Period Crossover, Positive Control study designed to evaluate the QT interval prolongation potential of 10 mg to 60 mg doses of APL-130277 compared to placebo and the positive control, 400mg moxifloxacin in subjects with Parkinson's Disease (PD) who experience motor fluctuations ("OFF" episodes) The patient is titrated to the highest tolerated dose from 10mg to 60mg, and then is randomized to one of six crossover sequences. Each sequence includes treatment with the following:
- Treatment A: APL-130277 at the dose determined in the Dose Titration Phase,
- Treatment B: Matched placebo,
- Treatment C: A single 400 mg dose of moxifloxacin
- Being tested
- APL-130277, Placebo, Moxifloxacin
- Keywords
- Parkinson's Disease, Off episodes
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APL-130277Drug
APL-130277 single dose
PlaceboDrug
Placebo single dose
MoxifloxacinDrug
moxifloxacin 400mg single dose
| Study group | Role | What they receive |
|---|---|---|
| APL-130277 | Experimental | APL-130277 at the dose determined in the dose titration phase Receives: Drug: APL-130277 |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
| moxifloxacin | Active comparator | moxifloxacin at a single 400mg dose Receives: Drug: Moxifloxacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time-Matched Change From Baseline in QTc, Placebo-Adjusted and Corrected for Heart Rate Based on the Fridericia Correction Method (QTcF) Using Delta Delta Method (ΔΔQTcF): Comparison Between APL-130277 and Placebo (Central Tendency Analysis)
For the primary central tendency analysis, the changes from baseline (ΔQTcF) were compared between APL-130277 and placebo (ΔΔQTcF). Baseline was defined as the mean of the 9 ECGs (3 sets of triplicate ECGs) recorded at baseline (P1V1). In case any of the 9 ECGs were missing, the baseline was defined as the mean of the available baseline values. The post-dose ECGs were evaluated at 15, 30, 45 and 60 minutes (mins) and 2, 3 and 4 hours post-dose at each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase. For each of the time points, an average value was calculated based on the 3 (or all available) ECGs. These average values were used in all change from baseline calculations.
Measured: Baseline to 15, 30, 45, 60 mins and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits.
Time-Matched Change From Baseline in QTc, Placebo-Adjusted and Corrected for Heart Rate Based on QTcF Using ΔΔQTcF: Comparison Between Moxifloxacin and Placebo (Assay Sensitivity Analysis)
For the assay sensitivity analysis in support of the primary central tendency analysis, the changes from baseline (ΔQTcF) were compared between moxifloxacin (positive control) and placebo (ΔΔQTcF). Baseline was defined as the mean of the 9 ECGs (3 sets of triplicate ECGs) recorded at baseline (P1V1). In case any of the 9 ECGs were missing, the baseline was defined as the mean of the available baseline values. The post-dose ECGs were evaluated at 60 mins and 2, 3 and 4 hours post-dose for each of the 3 treatment period dosing visits in the Randomized Crossover Assessment Phase. For each of the time points, an average value was calculated based on the 3 (or all available) ECGs. These average values were used in all change from baseline calculations.
Measured: Baseline to 60 mins and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits.
Secondary outcomes (12)
Cmax of Apomorphine and Apomorphine Sulfate (Metabolite) Following the Administration of APL-130277
The maximum observed plasma concentration (Cmax) for apomorphine and apomorphine sulfate (metabolite) was determined in patients treated with APL-130277. Pharmacokinetic (PK) parameters were derived using a non-compartmental analysis method. Bioanalysis of apomorphine and apomorphine-sulfate plasma concentration were measured using a validated liquid chromatography-tandem mass spectrometry (LC/MS-MS) method. The calibration range was 0.0200 nanograms per milliliter (ng/mL) to 20.0 ng/mL apomorphine and 10.0 to 1000 ng/mL apomorphine sulfate (metabolite). PK assessments were performed at each period of the Randomized Crossover Assessment Phase (at P1V1, P2V2 and P3V3) and results are presented for each of the APL-130277 doses administered (as determined for each patient during the Dose Titration Phase).
Measured: Blood samples for PK assessments were taken prior to dosing and at 0.5, 0.75, 1, 2, and 4 hours post-dose.
Tmax of Apomorphine and Apomorphine Sulfate (Metabolite) Following the Administration of APL-130277
The time of maximum observed plasma concentration (Tmax) for apomorphine and apomorphine sulfate (metabolite) was determined in patients treated with APL-130277. PK parameters were derived using a non-compartmental analysis method. Bioanalysis of apomorphine and apomorphine-sulfate plasma concentration were measured using a validated LC/MS-MS method. The calibration range was 0.0200 ng/mL to 20.0 ng/mL apomorphine and 10.0 to 1000 ng/mL apomorphine sulfate. PK assessments were performed at each period of the Randomized Crossover Assessment Phase (at P1V1, P2V2 and P3V3) and results are presented for each of the APL-130277 doses administered (as determined for each patient during the Dose Titration Phase).
Measured: Blood samples for PK assessments were taken prior to dosing and at 0.5, 0.75, 1, 2, and 4 hours post-dose.
AUClast of Apomorphine and Apomorphine Sulfate (Metabolite) Following the Administration of APL-130277
The area under the concentration-time curve from time of dosing to the last measurable point (AUClast) for apomorphine and apomorphine sulfate (metabolite) was determined in patients treated with APL-130277. PK parameters were derived using a non-compartmental analysis method. Bioanalysis of apomorphine and apomorphine-sulfate plasma concentration were measured using a validated LC/MS-MS method. The calibration range was 0.0200 ng/mL to 20.0 ng/mL apomorphine and 10.0 to 1000 ng/mL apomorphine sulfate. PK assessments were performed at each period of the Randomized Crossover Assessment Phase (at P1V1, P2V2 and P3V3) and results are presented for each of the APL-130277 doses administered (as determined for each patient during the Dose Titration Phase).
Measured: Blood samples for PK assessments were taken prior to dosing and at 0.5, 0.75, 1, 2, and 4 hours post-dose.
Number of Patients With Treatment-Emergent Adverse Events (TEAEs)
AE definition: any untoward medical occurrence in a clinical trial participant. Serious AE definition: an AE that is fatal, life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in permanent (persistent) disability/incapacity, is a congenital anomaly/birth defect or is an important medical event. Severity of AEs were classified as: mild: causes no limitation of usual activities, moderate: causes some limitation of usual activities; or severe: prevents or severely limits usual activities. The investigator assessed AEs for relatedness to study medication. TEAEs were defined as all AEs that started on or after the first dose of study medication (APL-130277, moxifloxacin or placebo). Results are presented for TEAEs during the Randomized Crossover Assessment Phase.
Measured: From first dose of study medication up to last study visit for Randomized Crossover Assessment Phase, approximately up to 2 weeks
ECG Assessments: Mean Change From Baseline to Post-Baseline Value for QTcB Interval During Randomized Crossover Assessment Phase
QTcB was defined as QT interval corrected with Bazett's method. QT was defined as time between start of Q wave and end of T wave. QTcB was determined during continuous 12-lead ECG (Holter) monitoring at each of the 3 treatment period dosing visits at pre-specified timepoints post-dose. Baseline was defined as the mean of the 9 ECGs (3 sets of triplicate ECGs) recorded at baseline (pre-dose P1V1). In case any of the 9 ECGs were missing, the baseline was defined as the mean of the available baseline values. The post-dose ECGs were evaluated at 15, 30, 45 and 60 mins and 2, 3 and 4 hours post-dose at each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase. For each of the time points, an average value was calculated based on the 3 (or all available) ECGs. Results are presented for the mean change from baseline at each pre-specified post-dose timepoint.
Measured: Baseline and at 15, 30, 45, 60 minutes and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase.
Mean Change From Pre-Dose to Post-Baseline Value in the Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III Motor Examination (MDS-UPDRS Part III) Score During the Dose Titration Phase
The Motor Function section (Part III) of the MDS-UPDRS was administered by the Investigator, and included 33 scores based on 18-items, each anchored with 5 responses: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range was from 0 to 132, with a lower score indicating better motor function and a higher score indicating more severe motor symptoms.
The least squares mean change in the MDS-UPDRS Part III score from pre-dose to 30, 60 and 90 minutes post-dose during the Dose Titration Phase at the highest tolerated APL-130277 dose level (indicated as Day 2) and the lowest APL-130277 dose resulting in a full 'ON' (indicated as Day 1) are presented.
Measured: Baseline (pre-dose) and at 30, 60 and 90 minutes after dosing during the Dose Titration Phase.
Median Time to 'ON' During the Dose Titration Phase
The time to 'ON' was calculated as minutes from the time when the patient received APL-130277 until the time the patient turned fully 'ON', as assessed by the Investigator. Data was censored at 90 minutes.
The median time to a full 'ON' response during the Dose Titration Phase following the highest tolerated APL-130277 dose level (indicated as Day 2) and the lowest APL-130277 dose resulting in a full 'ON' (indicated as Day 1) are presented. The median time to 'ON' on Day 1 and Day 2 was calculated using the Kaplan-Meier method.
Measured: Time of dosing up to 90 minutes post-dose during the Dose Titration Phase.
Median Duration of 'ON' During the Dose Titration Phase
The duration of 'ON' was calculated as minutes from the time when the patient turned fully 'ON' until the time when the patient turned 'OFF', as assessed by the Investigator. If the patient did not turn fully 'ON' within 90 minutes the duration of 'ON' was defined as zero minutes. If the patient turned fully 'ON' and did not turn 'OFF' by 90 minutes, the data was censored at 90 minutes minus the time when the patient turned fully 'ON'.
The median duration of a full 'ON' response during the Dose Titration Phase following the highest tolerated APL-130277 dose level (indicated as Day 2) and the lowest APL-130277 dose resulting in a full 'ON' (indicated as Day 1) are presented. The median duration of 'ON' on Day 1 and Day 2 was calculated using the Kaplan-Meier method.
Measured: Time of dosing up to 90 minutes post-dose during the Dose Titration Phase.
ECG Assessments: Mean Change From Baseline to Post-Baseline Value for Heart Rate During Randomized Crossover Assessment Phase
Heart rate was determined during continuous 12-lead ECG (Holter) monitoring at each of the 3 treatment period dosing visits at pre-specified timepoints post-dose. Baseline was defined as the mean of the 9 ECGs (3 sets of triplicate ECGs) recorded at baseline (pre-dose P1V1). In case any of the 9 ECGs were missing, the baseline was defined as the mean of the available baseline values. The post-dose ECGs were evaluated at 15, 30, 45 and 60 mins and 2, 3 and 4 hours post-dose at each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase. For each of the time points, an average value was calculated based on the 3 (or all available) ECGs. Results are presented for the mean change from baseline at each pre-specified post-dose timepoint.
Measured: Baseline and at 15, 30, 45, 60 minutes and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase.
ECG Assessments: Mean Change From Baseline to Post-Baseline Value for PR Interval During Randomized Crossover Assessment Phase
PR interval was defined as time from the onset of the P wave to the start of the QRS complex. PR interval was determined during continuous 12-lead ECG (Holter) monitoring at each of the 3 treatment period dosing visits at pre-specified timepoints post-dose. Baseline was defined as the mean of the 9 ECGs (3 sets of triplicate ECGs) recorded at baseline (pre-dose P1V1). In case any of the 9 ECGs were missing, the baseline was defined as the mean of the available baseline values. The post-dose ECGs were evaluated at 15, 30, 45 and 60 mins and 2, 3 and 4 hours post-dose at each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase. For each of the time points, an average value was calculated based on the 3 (or all available) ECGs. Results are presented for the mean change from baseline at each pre-specified post-dose timepoint.
Measured: Baseline (pre-dose P1V1) and at 15, 30, 45, 60 minutes and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase.
ECG Assessments: Mean Change From Baseline to Post-Baseline Value for QRS Interval During Randomized Crossover Assessment Phase
QRS interval was defined as the time of QRS complex (Q, R, and S waves). QRS interval was determined during continuous 12-lead ECG (Holter) monitoring at each of the 3 treatment period dosing visits at pre-specified timepoints post-dose. Baseline was defined as the mean of the 9 ECGs (3 sets of triplicate ECGs) recorded at baseline (pre-dose P1V1). In case any of the 9 ECGs were missing, the baseline was defined as the mean of the available baseline values. The post-dose ECGs were evaluated at 15, 30, 45 and 60 mins and 2, 3 and 4 hours post-dose at each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase. For each of the time points, an average value was calculated based on the 3 (or all available) ECGs. Results are presented for the mean change from baseline at each pre-specified post-dose timepoint.
Measured: Baseline and at 15, 30, 45, 60 minutes and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase.
ECG Assessments: Mean Change From Baseline to Post-Baseline Value for Uncorrected QT Interval During Randomized Crossover Assessment Phase
Uncorrected QT interval was defined as time between start of Q wave and end of T wave. QT interval was determined during continuous 12-lead ECG (Holter) monitoring at each of the 3 treatment period dosing visits at pre-specified timepoints post-dose. Baseline was defined as the mean of the 9 ECGs (3 sets of triplicate ECGs) recorded at baseline (pre-dose P1V1). In case any of the 9 ECGs were missing, the baseline was defined as the mean of the available baseline values. The post-dose ECGs were evaluated at 15, 30, 45 and 60 mins and 2, 3 and 4 hours post-dose at each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase. For each of the time points, an average value was calculated based on the 3 (or all available) ECGs. Results are presented for the mean change from baseline at each pre-specified post-dose timepoint.
Measured: Baseline and at 15, 30, 45, 60 minutes and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2017
- Study start3 Aug 2017
- Primary completion21 Dec 2017
- Study completion21 Dec 2017
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 Parkinson's DiseaseStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sumitomo Pharma America, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- CNS Medical Director, Study chair, Sunovion Pharmacetuicals Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03187301
- Sponsor's protocol ID
- CTH-201
- Other IDs
- 2016-001762-29, 2016
- Status last verified
- Jul 2020
- First submitted
- 7 Jun 2017
- Last updated
- 10 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Stocchi F, Peckham EL, De Pandis MF, Sciarappa K, Kleiman R, Agbo F, Olanow CW, Blum D, Navia B. A Randomized Thorough QT Study of Apomorphine Sublingual Film in Patients With Parkinson's Disease. Clin Pharmacol Drug Dev. 2022 Sep;11(9):1068-1077. doi: 10.1002/cpdd.1147. Epub 2022 Jul 28.
PubMed 35899977
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-Blind, Placebo Controlled, 3-Period Crossover, Positive Control, QT-Evaluation Study of APL-130277 in Subjects With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes)
- ClinicalTrials.gov ID
- NCT03187301
- Acronym / sponsor ID
- CTH-201
- Keywords
- Parkinson's Disease, Off episodes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Sumitomo Pharma America, Inc.Industry (pharma, biotech, devices)
- Study start
- 3 Aug 2017 (actual)
- Primary completion
- 21 Dec 2017 (actual)
- Study completion
- 21 Dec 2017 (actual)
- First posted
- 14 Jun 2017 (actual)
- Results
- Posted 10 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A cardiac safety study of an investigational drug to see how it affects the heart in people with Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes)
Detailed description
This multi-center, Phase 2, Randomized, Double-Blind, Placebo Controlled, 3-Period Crossover, Positive Control study designed to evaluate the QT interval prolongation potential of 10 mg to 60 mg doses of APL-130277 compared to placebo and the positive control, 400mg moxifloxacin in subjects with Parkinson's Disease (PD) who experience motor fluctuations ("OFF" episodes) The patient is titrated to the highest tolerated dose from 10mg to 60mg, and then is randomized to one of six crossover sequences. Each sequence includes treatment with the following:
- Treatment A: APL-130277 at the dose determined in the Dose Titration Phase,
- Treatment B: Matched placebo,
- Treatment C: A single 400 mg dose of moxifloxacin
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| APL-130277 | Experimental | Drug: APL-130277APL-130277 at the dose determined in the dose titration phase |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
| moxifloxacin | Active comparator | Drug: Moxifloxacinmoxifloxacin at a single 400mg dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 1) Male or female ≥ 18 years of age. 2) Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank Criteria (excluding the "more than one affected relative" criterion).
- 3) Clinically meaningful response to Levodopa (L-Dopa). Subjects with or without well defined "OFF" episodes, as determined by the Investigator will be allowed.
- 4) Receiving stable doses of L-Dopa/carbidopa (immediate or sustained release) administered at least 3 times per day OR Rytary™ administered 3 times per day, for at least 4 weeks before the initial Screening Visit (SV1). Subjects receiving L-Dopa/carbidopa 3 times a day must also be on stable treatment with adjunctive PD medication regimens. These regimens bust me maintained at a stable dose for at least 4 weeks prior to the initial Screening Visit (SV1) with the exception that MAO-B inhibitors must be maintained at a stable level for at least 8 weeks prior to the initial Screening Visit (SV1).
- 5) No planned medication change(s) or surgical intervention anticipated during the course of study.
- 6) the subject must be able to have a drug withdrawal induced "OFF" episode.
Key exclusion criteria (29 listed)
- Atypical or secondary parkinsonism
- Nausea associated with the use of dopamine agonists that requires treatment with an antiemetic.
- Previous treatment with any of the following: a neurosurgical procedure for PD; continuous subcutaneous (s.c.) apomorphine infusion; or Duodopa/Duopa.
- Treatment with any form of s.c. apomorphine within 7 days prior to the initial Screening Visit (SV1). Subjects that stopped s.c. apomorphine for any reason other than systemic safety concerns or lack of efficacy may be considered.
- Contraindications to moxifloxacin or APOKYN®, or hypersensitivity to apomorphine hydrochloride or any macrolide antibiotic or any of the ingredients of APOKYN® (notably sodium metabisulfite).
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 |
|---|---|---|
| APL-130277APL-130277 single dose | Drug | APL-130277 |
| PlaceboPlacebo single dose | Drug | Placebo |
| Moxifloxacinmoxifloxacin 400mg single dose | Drug | moxifloxacin |
Primary outcome
Time-Matched Change From Baseline in QTc, Placebo-Adjusted and Corrected for Heart Rate Based on the Fridericia Correction Method (QTcF) Using Delta Delta Method (ΔΔQTcF): Comparison Between APL-130277 and Placebo (Central Tendency Analysis)
Time frame: Baseline to 15, 30, 45, 60 mins and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits.
For the primary central tendency analysis, the changes from baseline (ΔQTcF) were compared between APL-130277 and placebo (ΔΔQTcF). Baseline was defined as the mean of the 9 ECGs (3 sets of triplicate ECGs) recorded at baseline (P1V1). In case any of the 9 ECGs were missing, the baseline was defined as the mean of the available baseline values. The post-dose ECGs were evaluated at 15, 30, 45 and 60 minutes (mins) and 2, 3 and 4 hours post-dose at each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase. For each of the time points, an average value was calculated based on the 3 (or all available) ECGs. These average values were used in all change from baseline calculations.
Time-Matched Change From Baseline in QTc, Placebo-Adjusted and Corrected for Heart Rate Based on QTcF Using ΔΔQTcF: Comparison Between Moxifloxacin and Placebo (Assay Sensitivity Analysis)
Time frame: Baseline to 60 mins and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits.
For the assay sensitivity analysis in support of the primary central tendency analysis, the changes from baseline (ΔQTcF) were compared between moxifloxacin (positive control) and placebo (ΔΔQTcF). Baseline was defined as the mean of the 9 ECGs (3 sets of triplicate ECGs) recorded at baseline (P1V1). In case any of the 9 ECGs were missing, the baseline was defined as the mean of the available baseline values. The post-dose ECGs were evaluated at 60 mins and 2, 3 and 4 hours post-dose for each of the 3 treatment period dosing visits in the Randomized Crossover Assessment Phase. For each of the time points, an average value was calculated based on the 3 (or all available) ECGs. These average values were used in all change from baseline calculations.
12 secondary outcomes
Cmax of Apomorphine and Apomorphine Sulfate (Metabolite) Following the Administration of APL-130277
Time frame: Blood samples for PK assessments were taken prior to dosing and at 0.5, 0.75, 1, 2, and 4 hours post-dose.
Tmax of Apomorphine and Apomorphine Sulfate (Metabolite) Following the Administration of APL-130277
Time frame: Blood samples for PK assessments were taken prior to dosing and at 0.5, 0.75, 1, 2, and 4 hours post-dose.
AUClast of Apomorphine and Apomorphine Sulfate (Metabolite) Following the Administration of APL-130277
Time frame: Blood samples for PK assessments were taken prior to dosing and at 0.5, 0.75, 1, 2, and 4 hours post-dose.
Number of Patients With Treatment-Emergent Adverse Events (TEAEs)
Time frame: From first dose of study medication up to last study visit for Randomized Crossover Assessment Phase, approximately up to 2 weeks
ECG Assessments: Mean Change From Baseline to Post-Baseline Value for QTcB Interval During Randomized Crossover Assessment Phase
Time frame: Baseline and at 15, 30, 45, 60 minutes and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase.
Mean Change From Pre-Dose to Post-Baseline Value in the Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III Motor Examination (MDS-UPDRS Part III) Score During the Dose Titration Phase
Time frame: Baseline (pre-dose) and at 30, 60 and 90 minutes after dosing during the Dose Titration Phase.
Median Time to 'ON' During the Dose Titration Phase
Time frame: Time of dosing up to 90 minutes post-dose during the Dose Titration Phase.
Median Duration of 'ON' During the Dose Titration Phase
Time frame: Time of dosing up to 90 minutes post-dose during the Dose Titration Phase.
ECG Assessments: Mean Change From Baseline to Post-Baseline Value for Heart Rate During Randomized Crossover Assessment Phase
Time frame: Baseline and at 15, 30, 45, 60 minutes and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase.
ECG Assessments: Mean Change From Baseline to Post-Baseline Value for PR Interval During Randomized Crossover Assessment Phase
Time frame: Baseline (pre-dose P1V1) and at 15, 30, 45, 60 minutes and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase.
ECG Assessments: Mean Change From Baseline to Post-Baseline Value for QRS Interval During Randomized Crossover Assessment Phase
Time frame: Baseline and at 15, 30, 45, 60 minutes and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase.
ECG Assessments: Mean Change From Baseline to Post-Baseline Value for Uncorrected QT Interval During Randomized Crossover Assessment Phase
Time frame: Baseline and at 15, 30, 45, 60 minutes and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits during the Randomized Crossover Assessment Phase.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35899977Stocchi F, Peckham EL, De Pandis MF, Sciarappa K, Kleiman R, Agbo F, Olanow CW, Blum D, Navia B. A Randomized Thorough QT Study of Apomorphine Sublingual Film in Patients With Parkinson's Disease. Clin Pharmacol Drug Dev. 2022 Sep;11(9):1068-1077. doi: 10.1002/cpdd.1147. Epub 2022 Jul 28.
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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.
CNS Medical Director study chair
Sunovion Pharmacetuicals Inc.
15 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing APL-130277 and Moxifloxacin in people with Parkinson's Disease and Off Episodes of Parkinson Disease, run by Sumitomo Pharma America, Inc. at 15 sites in 2 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 21 inclusion and 29 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 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, Italy. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 10 Aug 2020). 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?
Time-Matched Change From Baseline in QTc, Placebo-Adjusted and Corrected for Heart Rate Based on the Fridericia Correction Method (QTcF) Using Delta Delta Method (ΔΔQTcF): Comparison Between APL-130277 and Placebo (Central Tendency Analysis) (time frame: Baseline to 15, 30, 45, 60 mins and 2, 3, and 4 hours post-dose for each of the 3 treatment period dosing visits.). 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?
On the ClinicalTrials.gov record for NCT03187301, 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 Aug 2020.