Clinical trial NCT01650324: A Single-dose Phase 1 Study of DBPR108 in Healthy Male Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Keywords: DBPR108
DPP4
Diabetes
GLP-1
Incretins
Lead sponsor: National Health Research Institutes, Taiwan
Sponsor class: OTHER
First posted: 2012-07-26
Enrollment: 32
Sex: MALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: Adverse events were collected from Day -1 (baseline) through the end of the study, up to Day 7.
Secondary outcomes:
measure: Profile of Pharmacokinetics - Area Under the Plasma Concentration-Time Curve (AUC From 0 to Infinity)
timeFrame: predose (0 hr), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hrs post dose
measure: Profile of Pharmacokinetics - Observed Maximum Plasma Concentration (Cmax)
timeFrame: predose (0 hr), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hrs post dose
measure: Profile of Pharmacokinetics - Time of Maximum Plasma Concentration (Tmax)
timeFrame: predose (0 hr), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hrs post dose
measure: Change of Dipeptidyl Peptidase 4 (DPP4) Activities Between 48 Hrs Post Dose and 0 hr Predose
timeFrame: predose (0 hr) and 48 hrs post dose
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Taipei Medical University - Wanfang Hospital
Study officials:
References: