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Completed

NCT Number: NCT04829786

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.

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Key information

Conditions

FOP

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • 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:

  • 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.

Key Exclusion Criteria:

  • 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).
  • 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.

Treatment and study plan

palovarotene low-dose

Drug

oral capsules

palovarotene high-dose

Drug

oral capsules

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

Sponsors and collaborators

Lead sponsor

Clementia Pharmaceuticals Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2015
Primary completion
2015
Study completion
2015
First posted
Apr 2, 2021
Registry last updated
Apr 2, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.