A Single-dose Phase 1 Study of DBPR108 in Healthy Male Subjects

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Double-blind, Randomized, Placebo-controlled, Dose-ranging, Single-dose Study of the Safety, Pharmacokinetics, and Pharmacodynamics of DBPR108 in Healthy Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01650324
• Other study ID #: DBPR108-101
• Status: Completed
• Phase: Phase 1
• First received: July 19, 2012
• Last updated: August 15, 2014
• Start date: July 2012
• Est. completion date: December 2012

Study information

• Verified date: February 2014
• Source: National Health Research Institutes, Taiwan
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationTaiwan : Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The study is being performed to assess the safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) properties of single oral doses of DBPR108 in healthy male subjects.

Description:

This study represents the first administration of dipeptidyl peptidase 4 (DPP4) inhibitor DBPR108 to humans to evaluate the safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) properties following single oral doses in healthy subjects.

DPP4 is a validated drug target for the treatment of human type 2 diabetes. Objectives of the study will be to characterize the safety and tolerability of single doses of DBPR108; to characterize the single dose PK of DBPR108 in plasma and urine; to characterize the single dose PD of DBPR108 on glucose, glucagon, dipeptidyl peptidase 4 activity, and total and active forms of glucagon-like peptide-1 (GLP-1) in plasma levels and insulin and C-peptide in serum levels.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 45 Years

Eligibility

Inclusion Criteria:

• Male with suitable veins for cannulation or repeated venipuncture, and must be able to swallow the study drug intact;

• Aged between 20 and 45 years (inclusive) at the screening visit; and

• Able to provide written informed consent and willing to comply with the study protocol procedures and restrictions.

Exclusion Criteria:

• Has a body weight less than 50 kg and/or body mass index (BMI) less than 18 kg/m2 or greater than 30 kg/m2 at the screening visit;

• Has a creatinine clearance (Ccr) less than 80 mL/min at screening;

• Is not in good general health as judged by the Investigator based on routine medical history, vital signs, physical examination, ECG, laboratory tests, and urinalysis at the screening visit or at admission for the residential period;

• Is not normoglycemic defined as fasting glucose at less than 70 mg/dL (3.9 mmol/L) and greater than 100 mg/dL (5.5 mmol/L);

• Has a platelet count less than 150,000/µL;

• Uses any antihyperglycemic agents at screening or at admission for the residential period;

• Has a history or presence of any disease or condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs at the screening visit or at admission for the residential period;

• Has a clinically significant psychiatric, renal, hepatic, cardiovascular, gastrointestinal, or neurologic disease at screening or at admission for the residential period;

• Is a smoker and/or has used nicotine-containing products within the last 6 months prior to the screening for the current study and/or has a history of alcohol abuse;

• Has donated blood or participated in another clinical study within 8 weeks preceding the day of admission;

• Excessive intake of caffeine-containing drinks or food (ie, coffee, tea, chocolate, PAOLYTA B Liq, WHISBIH Liq, or cola [more than 6 units of caffeine per day]);

• Use of drugs with enzyme-inducing properties such as St. John's Wort within 4 weeks prior to the first administration of investigational product;

• Has used prescription or nonprescription medication (except for occasional use of paracetamol or nasal spray) or herbal remedies or vitamins or minerals within 2 weeks or 5 half-lives of the drug, whichever is longer, prior to dosing until end of study;

• Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first administration of investigational product;

• Male subjects who are unwilling to use barrier contraception in addition to having their partner use another method of contraception, for the duration of the study and for 3 months after dosing;

• Has a positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), or human immunodeficiency virus (HIV);

• Has received a blood transfusion and/or has HCV infection;

• Positive result on screening for drugs of abuse, alcohol, or cotinine (nicotine) at screening or admission; or

• Involved in the planning or conduct of the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• DBPR108
DBPR108 capsules in four doses beginning at 25 mg and rising to 600 mg.
• matching placebo
Matching placebo capsules in four doses beginning at 25 mg and rising to 600 mg.

Locations

Country	Name	City	State
Taiwan	Taipei Medical University - Wanfang Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Health Research Institutes, Taiwan

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events as a Measure of Safety and Tolerability	There were 4 mild adverse events observed during the course of study.	Adverse events were collected from Day -1 (baseline) through the end of the study, up to Day 7.	No
Secondary	Profile of Pharmacokinetics - Area Under the Plasma Concentration-Time Curve (AUC From 0 to Infinity)	Plasma samples were used to determine the AUC from time 0 to infinity for DBPR108. The placebo group is not included in the table below; this outcome measure only evaluated the DBPR108 groups.	predose (0 hr), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hrs post dose	No
Secondary	Profile of Pharmacokinetics - Observed Maximum Plasma Concentration (Cmax)	Plasma samples were used to determine the Cmax for DBPR108. The placebo group is not included in the table below; this outcome measure only evaluated the DBPR108 groups.	predose (0 hr), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hrs post dose	No
Secondary	Profile of Pharmacokinetics - Time of Maximum Plasma Concentration (Tmax)	Plasma samples were used to determine the Time of Maximum Plasma Concentration for DBPR108. The placebo group is not included in the table below; this outcome measure only evaluated the DBPR108 groups.	predose (0 hr), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hrs post dose	No
Secondary	Change of Dipeptidyl Peptidase 4 (DPP4) Activities Between 48 Hrs Post Dose and 0 hr Predose	Change of plasma DPP4 activity at 48 hrs post dose from predose (0 hr). The values were computed as areas under the DPP4 activity-time curve using ANCOVA model, in which the unit of the activity is pmol/min.	predose (0 hr) and 48 hrs post dose	No