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

Clementia Pharmaceuticals Inc.0 个研究点目标入组 18 人开始时间: 2015年9月1日最近更新: 2021年4月2日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Clementia Pharmaceuticals Inc.
入组人数: 18
主要终点: Elimination half-life

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

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.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Crossover
主要目的: Treatment
盲法: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

入排标准

年龄范围: 18 Years 至 55 Years（Adult）
性别: All
接受健康志愿者: 是

入选标准

•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.

排除标准

•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.

研究组 & 干预措施

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.

干预措施: palovarotene low-dose (Drug)

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.

干预措施: palovarotene high-dose (Drug)

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.

干预措施: palovarotene low-dose (Drug)

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.

干预措施: palovarotene high-dose (Drug)