Bioequivalence of Sitagliptin Phosphate/Metformin Hydrochloride Tablets in Healthy Chinese Subjects

Bioequivalence of Sitagliptin Phosphate/Metformin Hydrochloride Tablets in Healthy Chinese Subjects: A Single-dose and Two-period Crossover Study

An open-label, randomized, single-dose, two-period, two-group, crossover study was conducted in 48 healthy Chinese volunteers under fasted or fed conditions (24 volunteers for each condition) to assess the bioequivalence between two formulations of Sitagliptin Phosphate/metformin Hydrochloride Tablets.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Sitagliptin Phosphate/metformin Hydrochloride Tablets(JANUMET®,50mg/850mg); Drug: Sitagliptin Phosphate/metformin Hydrochloride Tablets (50mg/850mg)

Detailed Description

The single-dose randomized, open-label, two-period crossover study was executed in the Phase I Clinical Research Center of the Affiliated Hospital of Qingdao University. This study was conducted to assess the bioequivalence of Sitagliptin Phosphate/metformin Hydrochloride Tablets in healthy Chinese subjects and estimate the pharmacokinetics profiles of Sitagliptin Phosphate/metformin Hydrochloride Tablets. An open-label, randomized, single-dose, two-period, crossover study was conducted in 48 healthy Chinese volunteers under fasted or fed conditions (24 subjects for each condition) to assess the bioequivalence between two formulations of Sitagliptin Phosphate/metformin Hydrochloride Tablets. Blood samples were collected at specified time intervals, and the plasma concentrations of sitagliptin and metformin were determined by a validated liquid chromatography mass spectrum/ mass spectrum method. Pharmacokinetic and bioavailability parameters were estimated via non-compartmental methods. Adverse events were also recorded. If the 90% confidence intervals of the ratios of geometrical mean of test and reference formulations for Cmax, AUC0-t and AUC0-∞ are all within the predefined bioequivalence criteria range of 80%-125% for sitagliptin and metformin, the two formulations can be considered bioequivalent.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanndong
    • Qingdao, Shanndong, China, 266003
      • Phase I Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male or female aged between 18 and 45 years old (including the critical value).
• The body mass index is in the range of 19-28 kg/m2 (including the critical value). The weight of male is not less than 50 kg, and that of female is not less than 45 kg (including the critical value).
• Subjects who had not any medical history of cardiovascular, digestive, respiratory, nervous or hepatic/renal impairment. The following examination show that the indicators are normal or abnormal without clinical significance. The examination including: physical examination, 12-lead ECG, vital sign measurements, and laboratory safety tests.
• The subjects have no family planning within 6 months and could select contraceptive method.
• Before the study, all subjects have been informed of the study's purpose, protocol, benefits, and risks, and signed the informed consent voluntarily.
• The subjects could complete the study according to the protocol.

Exclusion Criteria:

• Being allergy to the study medications, smoking, alcohol abuse.
• Participation in another clinical trial within 3 months.
• Any history of hypersensitivity, needlesickness or idiosyncratic reactions to any food or drug;
• Any use of other prescription drugs (including contraceptive) 14 days prior to medication for this study;
• Any use of prescription or over-the-counter drugs, functional vitamin, herbal/ alcohol products, grapefruit-containing or caffeine/xanthine-rich food and beverages 48 h prior to medication for this study; dysphagia or having special dietary requirements;
• occurring acute disease in the screening period or before the medication lactating or pregnant women;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sitagliptin Phosphate/metformin Hydrochloride Tablets (JANUMET®); JANUMET®, 50mg/850mg, batch no. M047893, manufactured by MSD Pharma (Singapore) Pte.Ltd	Drug: Sitagliptin Phosphate/metformin Hydrochloride Tablets(JANUMET®,50mg/850mg); The subjects randomly received single oral administration of Sitagliptin Phosphate/metformin Hydrochloride Tablets (JANUMET®, 50mg/850mg)
Experimental: Sitagliptin Phosphate/metformin Hydrochloride Tablets; 50mg/850mg, batch no. 161006, manufactured by Tonghua Dongbao Pharmaceutical Co., Ltd.	Drug: Sitagliptin Phosphate/metformin Hydrochloride Tablets (50mg/850mg); The subjects randomly received single oral administration of Sitagliptin Phosphate/metformin Hydrochloride Tablets (50mg/850mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The ratios of geometrical mean	The two preparations were considered bioequivalent if the 90% CIs of the ratios of the primary pharmacokinetics parameters were within the predefined acceptance range of 80%-125%.	80 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The occurrence rate of adverse events	Adverse events were recorded to evaluate the safety of the studied drugs.	80 days

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Qingdao University
• Investigators: Principal Investigator: Yu Doctor Cao, the study director of phase I clinical research center

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2018
• Primary Completion (Actual): May 20, 2018
• Study Completion (Actual): July 31, 2018

Study Registration Dates

• First Submitted: April 26, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 7, 2021

Study Record Updates

• Last Update Posted (Actual): May 7, 2021
• Last Update Submitted That Met QC Criteria: May 5, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sitagliptin Phosphate
• Other Study ID Numbers: DBH061L012017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No