FOPPhase 1NCT04829786
Study to Compare the Pharmacokinetics, Safety, and Tolerability Following Administration of Palovarotene in Healthy Japanese and Non-Asian Subjects
A Phase 1 study testing palovarotene low-dose and palovarotene high-dose in people with FOP, run by Clementia Pharmaceuticals Inc..
Trial summary
this study purpose is to assess safety, tolerability and the pharmacokinetic (PK) profile of palovarotene in healthy Japanese and matched (with respect to sex, age, and weight) non-Asian subjects aged 18 to 55 years. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- FOP
- What is being tested?
- palovarotene low-dose and palovarotene high-dose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2015to 23 Oct 2015
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- The subject had a body mass index (BMI) of 18 to 30 kg/m2 and a body weight of 50 kg or more. Body mass index was calculated as follows: weight (kg)/height2 (m2).
- The subject had a resting (at least 5 minutes) sitting pulse of greater than 45 but less than 100 beats per minute (BPM) and systolic and diastolic blood pressure (BP) of less than 140/90 mmHg
- The subject was a nonsmoker for at least 6 months prior to the screening visit and had a maximum smoking history of 5-pack years
- The subject was in good general health as determined by medical history, physical examination, 12-lead ECG, vital signs, and clinical laboratory results obtained within 28 days prior to the start of the study.
- The subject had the ability to swallow an oral solid-dosage form of medication
- Non-Asian Subjects:
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- The subject must have had both biological parents and four biological grandparents of non-Asian descent.
- The subject must have been matched individually (on a 1:1 basis) with respect to sex, age (within 5 years), and weight (within 10%) to a Japanese subject.
- Japanese Subjects
- The subject must have been born in Japan and have both biological parents and four biological grandparents of Japanese descent.
- The subject had a valid Japanese passport.
- The subject must have lived outside of Japan for no more than 5 years.
- The subject must not have significantly changed their diet since leaving Japan, eg, he/she must mainly had been eating a "Japanese" diet.
Who cannot join
- The subject had a history or current evidence of a clinically significant or uncontrolled disease, including but not limited to: cardiovascular, hepatic, renal, hematological, neuropsychological, endocrine, gastrointestinal, reproductive, or pulmonary.
- The subject was pregnant, nursing, or planned to become pregnant or donate gametes (ova or sperm) for in vitro fertilization during the study period or for 30 days following the subject's last study-related visit (for eligible subjects only, if applicable).
- The subject had a medical condition that may have potentially been aggravated by a systemic retinoid such as isotretinoin or etretinate.
- The subject had been exposed to synthetic oral retinoids in the past 30 days prior to the screening visit (signature of the informed consent).
- The subject was currently using vitamin A or beta carotene, multivitamins containing vitamin A or beta carotene, or herbal preparations, fish oil, and was unable or unwilling to discontinue use of these products for the duration of the study.
- The subject had a history or presence of silent infections, including positive tests for human immunodeficiency virus type 1 (HIV-1), HIV-2, hepatitis B virus (HBV), or hepatitis C virus (HCV).
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- The subject had any disease or condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
- The subject had concurrent treatment with tetracycline due to the potential increased risk of pseudotumor cerebri.
- The subject had a history of allergy or hypersensitivity to retinoids or lactose.
- The subject had been exposed to any investigational drug within 30 days or six half-lives (whichever is greater) of the screening visit.
- The subject had been treated with any known CYP450 3A4 inhibitors (eg, ketoconazole, gestodene, rifampin) within 30 days prior to the screening visit.
- The subject had a history of alcohol and/or substance abuse.
- The subject was considered to be vulnerable (eg, cognitively impaired, a person kept in detention).
- Any reason that in the opinion of the Investigator would have led to the inability of the subject and/or family to comply with the protocol.
About this study
Official title: A Double-Blind, Randomized, Cross-Over Single-Dose Study to Compare the Pharmacokinetics, Safety, and Tolerability Following Administration of Palovarotene in Healthy Japanese and Non-Asian Subjects
this study purpose is to assess safety, tolerability and the pharmacokinetic (PK) profile of palovarotene in healthy Japanese and matched (with respect to sex, age, and weight) non-Asian subjects aged 18 to 55 years.
- Conditions
- FOP
- Being tested
- palovarotene low-dose, palovarotene high-dose
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
palovarotene low-doseDrug
oral capsules
palovarotene high-doseDrug
oral capsules
| Study group | Role | What they receive |
|---|---|---|
| Japanese group | Experimental | The subjects will receive in Period 1 either the low-dose or high-dose first, and in Period 2 they will receive the alternate dose. There is a washout period between periods. Receives: Drug: palovarotene low-dose; Drug: palovarotene high-dose |
| non-Asian group | Experimental | The subjects will receive in Period 1 either the low-dose or high-dose first, and in Period 2 they will receive the alternate dose. There is a washout period between periods. Receives: Drug: palovarotene low-dose; Drug: palovarotene high-dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum (peak) plasma drug concentration
Measured: pre-dose (0 hour), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours post-drug administration.
Time to reach maximum (peak) plasma concentration following drug administration
Measured: pre-dose (0 hour), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours post-drug administration.
Area under the plasma concentration time curve from time zero to the last quantifiable time point, calculated by linear-log trapezoidal summation
Measured: pre-dose (0 hour), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours post-drug administration.
Area under the plasma concentration time curve from time zero to infinity, calculated by linear-log trapezoidal summation and extrapolated to infinity by addition of the last quantifiable plasma concentration divided by the elimination rate constant
Measured: pre-dose (0 hour), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours post-drug administration.
Terminal disposition rate constant/terminal rate constant, determined by linear regression of the terminal points of the log-linear plasma concentration-time curve
Measured: pre-dose (0 hour), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours post-drug administration.
Elimination half-life
Measured: pre-dose (0 hour), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours post-drug administration.
Apparent volume of distribution after non-intravenous (oral) administration
Measured: pre-dose (0 hour), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours post-drug administration.
Apparent total clearance of the drug from plasma after oral administration calculated by dose/ AUC(0-∞)
Measured: pre-dose (0 hour), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours post-drug administration.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2021
- Study start1 Sep 2015
- Primary completion23 Oct 2015
- Study completion23 Oct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for FOPStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- The subjects will be randomized to receive in Period 1 either the low-dose or high-dose first, and in Period 2 they received the alternate dose.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clementia Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ipsen Medical Director, Study director, Ipsen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04829786
- Sponsor's protocol ID
- PVO-1A-101
- Status last verified
- Apr 2021
- First submitted
- 1 Apr 2021
- Last updated
- 2 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Randomized, Cross-Over Single-Dose Study to Compare the Pharmacokinetics, Safety, and Tolerability Following Administration of Palovarotene in Healthy Japanese and Non-Asian Subjects
- ClinicalTrials.gov ID
- NCT04829786
- Acronym / sponsor ID
- PVO-1A-101
- Conditions
- FOP
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Clementia Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Sep 2015 (actual)
- Primary completion
- 23 Oct 2015 (actual)
- Study completion
- 23 Oct 2015 (actual)
- First posted
- 2 Apr 2021 (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 study purpose is to assess safety, tolerability and the pharmacokinetic (PK) profile of palovarotene in healthy Japanese and matched (with respect to sex, age, and weight) non-Asian subjects aged 18 to 55 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The subjects will be randomized to receive in Period 1 either the low-dose or high-dose first, and in Period 2 they received the alternate dose.
| Arm | Type | Receives |
|---|---|---|
| Japanese group | Experimental | Drug: palovarotene low-dose, Drug: palovarotene high-doseThe subjects will receive in Period 1 either the low-dose or high-dose first, and in Period 2 they will receive the alternate dose. There is a washout period between periods. |
| non-Asian group | Experimental | Drug: palovarotene low-dose, Drug: palovarotene high-doseThe subjects will receive in Period 1 either the low-dose or high-dose first, and in Period 2 they will receive the alternate dose. There is a washout period between periods. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- The subject had a body mass index (BMI) of 18 to 30 kg/m2 and a body weight of 50 kg or more. Body mass index was calculated as follows: weight (kg)/height2 (m2).
- The subject had a resting (at least 5 minutes) sitting pulse of greater than 45 but less than 100 beats per minute (BPM) and systolic and diastolic blood pressure (BP) of less than 140/90 mmHg
- The subject was a nonsmoker for at least 6 months prior to the screening visit and had a maximum smoking history of 5-pack years
- The subject was in good general health as determined by medical history, physical examination, 12-lead ECG, vital signs, and clinical laboratory results obtained within 28 days prior to the start of the study.
- The subject had the ability to swallow an oral solid-dosage form of medication
Key exclusion criteria (14 listed)
- The subject had a history or current evidence of a clinically significant or uncontrolled disease, including but not limited to: cardiovascular, hepatic, renal, hematological, neuropsychological, endocrine, gastrointestinal, reproductive, or pulmonary.
- The subject was pregnant, nursing, or planned to become pregnant or donate gametes (ova or sperm) for in vitro fertilization during the study period or for 30 days following the subject's last study-related visit (for eligible subjects only, if applicable).
- The subject had a medical condition that may have potentially been aggravated by a systemic retinoid such as isotretinoin or etretinate.
- The subject had been exposed to synthetic oral retinoids in the past 30 days prior to the screening visit (signature of the informed consent).
- The subject was currently using vitamin A or beta carotene, multivitamins containing vitamin A or beta carotene, or herbal preparations, fish oil, and was unable or unwilling to discontinue use of these products for the duration of the study.
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 |
|---|---|---|
| palovarotene low-doseoral capsules | Drug | Japanese group, non-Asian group |
| palovarotene high-doseoral capsules | Drug | Japanese group, non-Asian group |
Primary outcome
Maximum (peak) plasma drug concentration
Time frame: pre-dose (0 hour), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours post-drug administration.
Time to reach maximum (peak) plasma concentration following drug administration
Time frame: pre-dose (0 hour), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours post-drug administration.
Area under the plasma concentration time curve from time zero to the last quantifiable time point, calculated by linear-log trapezoidal summation
Time frame: pre-dose (0 hour), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours post-drug administration.
Area under the plasma concentration time curve from time zero to infinity, calculated by linear-log trapezoidal summation and extrapolated to infinity by addition of the last quantifiable plasma concentration divided by the elimination rate constant
Time frame: pre-dose (0 hour), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours post-drug administration.
Terminal disposition rate constant/terminal rate constant, determined by linear regression of the terminal points of the log-linear plasma concentration-time curve
Time frame: pre-dose (0 hour), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours post-drug administration.
Elimination half-life
Time frame: pre-dose (0 hour), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours post-drug administration.
Apparent volume of distribution after non-intravenous (oral) administration
Time frame: pre-dose (0 hour), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours post-drug administration.
Apparent total clearance of the drug from plasma after oral administration calculated by dose/ AUC(0-∞)
Time frame: pre-dose (0 hour), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours post-drug administration.
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 2 Apr 2021.
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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.
Ipsen Medical Director study director
Ipsen
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing palovarotene low-dose and palovarotene high-dose in people with FOP, run by Clementia Pharmaceuticals Inc..
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 13 inclusion and 14 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 2 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
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 (peak) plasma drug concentration (time frame: pre-dose (0 hour), 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, and 72 hours post-drug administration.). The study lists 8 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 2 Apr 2021.