Comparative Pharmacokinetic Study of Ramelteon Modified-Release Tablets and Ramelteon Tablets in Healthy Subjects

NCT06890715 | Completed Phase 1 FDA Drug

• 1 other identifier: CTS-CO-2545
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

A randomized, open-label, two-period, double-crossover comparative pharmacokinetic (PK) study of a single oral dose of Ramelteon Modified-Release Tablets and Ramelteon Tablets in Chinese healthy subjects Primary objective: To evaluate the bioequivalence of the test product and the reference product by comparing their plasma concentrations and main PK parameters by oral administration in healthy Chinese subjects using Ramelteon Modified-Release Tablets (strength: 8 mg/tablet) developed by Overseas Pharmaceuticals, Ltd. as the test product and Ramelteon Tablets (trade name: Rozerem®, strength: 8 mg/tablet) produced by Takeda Pharmaceuticals America, Inc. as the reference product. Secondary objective: To evaluate the safety of Ramelteon Modified-Release Tablets (test product) and Ramelteon Tablets (reference product) with oral administration after drinking milk in healthy Chinese subjects.

Conditions

Chronic Insomnia Characterized

Keywords

Ramelteon; Modified-Release; Chronic insomnia characterized by difficulties in falling asleep or maintaining sleep; Healthy Volunteers

Outcome Measures

Primary Outcomes (3)

• Area under the curve from time zero to the time of the last quantifiable plasma concentration of the period (AUC0-last)

  The 90% CI for the geometric mean ratios (i.e., antilog-transformation for 90% CI of difference with log transformation) of AUC0-last within \[0.8, 1.25\] range will be used to determine the result of bioequivalence.

  1 month

• Peak concentration at each treatment period (Cmax,tp)

  The 90% CI for the geometric mean ratios (i.e., antilog-transformation for 90% CI of difference with log transformation)of Cmax,tp within \[0.8, 1.25\] range will be used to determine the result of bioequivalence.

  1 month

• Area under the curve from time zero to infinity (AUC0-inf)

  The 90% CI for the geometric mean ratios (i.e., antilog-transformation for 90% CI of difference with log transformation)of AUC0-inf within \[0.8, 1.25\] range will be used to determine the result of bioequivalence.

  1 month

Secondary Outcomes (3)

• Peak concentration of the first dosing (Cmax)

  1 month

• Time to reach peak concentration of the first dosing (Tmax)

  1 month

• Terminal half-life (T1/2)

  1 month

Study Arms (2)

Group T

EXPERIMENTAL

Test product (T): Ramelteon Modified-Release Tablets Strength: 8 mg/tablet Batch No.: G12308010 Content: 8 mg/tablet Valid to: 2025-8-16 Storage Conditions:Not higher than 25°C, sealed store Manufacturer: Overseas Pharmaceuticals, Ltd.

Drug: Test product (T): Ramelteon Modified-Release Tablets

Group R

ACTIVE COMPARATOR

Reference product (R): Ramelteon Tablets Strength: 8 mg/tablet Batch No.: 12216533 Content: 8 mg/tablet Valid to: 2024-10 Storage Conditions: 25 ° C (77°F) storage, allowing short-term temperature deviations of 15-30 ° C (59-86°F) Manufacturer:Takeda Pharmaceuticals America, Inc.

Drug: Reference product (R): Ramelteon Tablets

Interventions

Test product (T): Ramelteon Modified-Release Tablets DRUG

Oral, take 1 tablet at a time, once a day.

Group T

Reference product (R): Ramelteon Tablets DRUG

Oral, take 1 tablet at a time, once a day.

Group R

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female subjects aged 18 to 45 years (including 18 and 45 years);
• Male subjects with a body weight ≥ 50.0 kg, and female subjects with a body weight ≥ 45.0 kg; BMI (BMI = body weight (kg)/\[height (m)\]2) within the range of 19-26.0 kg/m2 (including the critical value);
• Subject who fully understands the purpose, nature, method and possible adverse reactions of the study, voluntarily acts as a subject, and signs informed consent prior to the commencement of any study procedure;;
• Subjects who are able to communicate well with the investigator and understand and adhere to the study requirements.

You may not qualify if:

• Subjects with an allergic history to the study drug or other melatonin or any other component of the study drug, or an allergic history to drug, food , pollen or a specific allergic history (asthma, allergic rhinitis);
• Subjects who have special dietary requirements and cannot accept a unified diet;
• Subjects with a history of dysphagia or any gastrointestinal disorder affecting drug absorption;
• Subjects who cannot tolerate venipuncture , or with needle fainting or blood collection difficulties;
• Subjects with clinically significant hematological, endocrine, cardiovascular, hepatic, renal and pulmonary disorders that may affect drug absorption, distribution, metabolism and excretion;
• Vital signs examination, physical examination, clinical laboratory examination (blood routine, urine routine, blood biochemistry, coagulation four, pregnancy test (female), etc.), 12-lead electrocardiogram, chest X-ray examination results judged by researchers to be clinically significant;
• Subjects with a surgical history within the 3 months prior to the study or taking the study drug or who plan to have surgery during the trial ；
• Those who received the vaccine within 28 days before the first dose； 9) Subjects with blood donation or massive blood loss (\> 450 mL) within 3 months before the study;
• \) Subjects taking special diet (including pitaya or grapefruit and products containing grapefruit ingredients) or having strenuous exercise within 7 days before taking the study drug, or having other factors affecting drug absorption, distribution, metabolism and excretion; 11) Subjects administered with any prescription drugs, over-the-counter, herbal, or health products within 14 days prior to taking the study drug; 12) Drug users with a history of interaction with rametylamine tablets within 30 days prior to screening (fluvoxamine, rifampicin, ketoconazole, fluconazole, Donepezil, doxepin, Zolpidem, etc.; 13) Regular drinkers within 6 months prior to the study, i.e., drinking more than 14 units of alcohol per week (1 unit = 360 mL of beer or 45 mL of spirit containing 40% alcohol or 150 mL of wine); 14) Subjects who have a history of smoking in the first 3 months of prior to screening; Or who cannot stop using any tobacco products during the test period; Or positive results of tobacco test; 15) Subjects who have consumed chocolate, any caffeine-containing, or xanthine-rich food or beverage, such as coffee, strong tea, and cola 48 h before taking the study drug; 16) Subjects having taken any alcohol-containing products within 48 h before taking the study drug, or having a positive result for alcohol screening; Subjects positive for drug screening or with a history of drug abuse within the past five years or using drugs 3 months before the trial; 17) Female subjects with positive pregnancy test or lactating during the screening period or during the trial;Subjects (including male subjects) had a birth plan or could not use effective contraception from 2 weeks before the trial screening to 1 month after the trial ended; 18) Subjects positive for HBsAg, HCV-Ab, anti-HIV or primary syphilis screening; 19) Subjects who have participated in other clinical trials and used experimental drugs or devices within 3 months prior to screening; 20) Subjects with underlying medical, psychiatric, psychological or other discomfort conditions, poor compliance, or who, as judged by the investigator, are not suitable for the study.

Sponsors & Collaborators

• Overseas Pharmaceuticals, Ltd.: lead
• Beijing CTSmed Co. Ltd: collaborator

Study Sites (1)

clinical trial centre of Medical ethics committee of Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, 510700, China

Location

Study Officials

• Shuai He Associate Chief Pharmacist, Doctor

  The Zhujiang Hospital of Southern Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2025
• First Posted: March 24, 2025
• Study Start: June 24, 2024
• Primary Completion: July 2, 2024
• Study Completion: July 8, 2024
• Last Updated: March 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)