Study Evaluating Safety, Tolerability, And Action Of OAP-189 In Subjects With Type 2 Diabetes On Metformin

Study Overview
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Brief Summary
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This is a study to evaluate the safety, tolerability, and activity of OAP-189 in subjects with type 2 diabetes who are taking metformin for their diabetes.

Official Title
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A RANDOMIZED, PARALLEL-GROUP, OPEN-LABEL, PLACEBO CONTROLLED STUDY OF THE EFFECT OF OAP-189 ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF METFORMIN IN DIABETIC SUBJECTS.

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: OAP-189
* Drug: placebo comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have been diagnosed with type 2 diabetes, with HbA1c level >=7.0% and <=11.0% and a fasting glucose level <=280 mg/dL. Men or women of nonchildbearing potential (WONCBP), aged 18 to 65 years inclusive on study day 1. Body mass index in the range of 27 to 40kg/m² (inclusive) and body weight >=50 kg. Subjects must be otherwise generally healthy, but may be enrolled with a stable chronic illness, if it is well controlled and does not interfere with the primary objective of the study. Subjects must currently be treated for diabetes with metformin alone at a total daily dose of >=1gm (administered QD or BID) and that dose must have been stable for at least 4 weeks before study day 1. Nonsmoker. Exclusion Criteria: Any significant disease with the exception of diabetes mellitus. Any surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the investigational product. Acute disease state (eg, nausea, vomiting, fever, or diarrhea) within 7 days before study day 1. Any clinically important problems in physical examination results, vitals sign measurements, ECGs, or clinical laboratory test results. Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies. Positive findings of urine drug screen Use of any investigational or non-permitted prescription drug within 30 days before investigational product administration.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: OAP-189<br> | Drug: OAP-189<br>* Group 1: OAP-189 BID (0.2 mg BID) x 7 days Group 2: OAP-189 (0.4 mg BID) x 7 days Group 3: OAP-189 QD (0.9 mg x 7 days followed by 1.2 mg x 7 days; MR formulation) Group 4: OAP-189 QD (1.2 mg x 7 days followed by 1.6 mg x 7 days; MR formulation) Group 5: OAP-189 QD (1.2 mg x 7 days followed by 1.6 mg x 7 days; different MR formulation) Group 6: OAP-189 QD (1.2 mg x 7 days followed by 1.6 mg x 7 days; different MR formulation)<br>|
| Placebo Comparator: 2<br> | Drug: placebo comparator<br>* Group 1 & 2: PBO x 7 days BID Group 3: PBO QD x 14 days Group 4: PBO QD x 14 days Group 5: PBO QD x 14 days Group 6: PBO QD x 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinically Significant Physical Examination Abnormalities | Physical examination included examination of skin, head, eyes, ears, nose, throat (HEENT), heart, lungs, abdomen, extremities, neurological function, back and lymph nodes. Clinically significant physical examination abnormalities were considered as adverse events based on investigator's discretion. | Baseline up to 17 days after last dose of study drug (Day 31) | 
| Number of Participants With Clinically Significant Vital Signs Abnormalities | Criteria for clinically significant vital sign abnormalities: sitting systolic blood pressure (SBP) of (greater than equal to) >=160 millimeter of mercury (mmHg), (less than equal to) <=90 mmHg, >=20 mmHg increase and decrease from baseline; sitting diastolic blood pressure (DBP) of >=100 mmHg, <=50 mmHg, >=15 mmHg increase and decrease from baseline; heart rate of >=120 beats per minute (bpm), <=45 bpm, (greater than) >15 bpm increase and decrease from baseline, orthostatic SBP: decrease of >=20 mm Hg from sitting value, orthostatic DBP: decrease of >=20 mm Hg from sitting value, orthostatic heart rate: increase of >=30 bpm from sitting value, oral temperature of (less than) <35 or >38.3 degree celsius, respiratory rate of <10 or >25 breaths per minute, weight: maximum increase or decrease of >=7 percent (%) from baseline. | Baseline up to 17 days after last dose of study drug (Day 31) | 
| Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities | Criteria for clinically significant ECG abnormalities: PR interval >=220 millisecond (msec) or a change of >=20 msec from baseline values, QRS interval >=120 msec, QTc interval >450 msec (in males) and >470 msec (in females). | Baseline up to 17 days after last dose of study drug (Day 31) | 
| Number of Participants With Clinically Significant Laboratory Abnormalities | Hematocrit, haemoglobin: decrease of >=0.05 L/L and >=20 g/L from baseline respectively, WBC count:<3*10^9 /L, neutrophils: <1.5*10^9 /L, platelet count: <100*10^9 /L, eosinophil: <0.5*10^9 /L; prothrombin time, partial thromboplastin time >1.5*upper limit of normal (ULN); sodium:>5 mmol/L above ULN or below lower limit of normal(LLN), potassium >0.5 mmol/L above ULN or below LLN, creatinine >1.36*ULN, blood urea nitrogen >1.5*ULN, glucose (fasting) >0.83 mmol/L above ULN or below LLN, glucose (non-fasting) >5 mmol/L above ULN or >0.56 below LLN, calcium, magnesium: Change of >=0.25 and >=0.21 mmol/L from baseline respectively, phosphorus >0.162 mmol/L above ULN or below LLN, total protein, albumin, uric acid: change of >=20g/L, >=10 g/L, >0.119 mmol/L from baseline respectively, creatinine kinase >3*ULN, total cholesterol >7.77 mmol/L, triglycerides >3.39 mmol/L: AST, ALT, total bilirubin >2*ULN, alkaline phosphatase >1.5*ULN, alpha-glumatyl transferase, lactate dehydrogenase >3*ULN. | Baseline up to 17 days after last dose of study drug (Day 31) | 
| Number of Participants With Injection Site Reactions | Injection site reactions included irritation, erythema, pain, hematoma, inflammation. | Baseline up to 17 days after last dose of study drug (Day 31) | 
| Number of Participants With Clinically Significant Fasting Glucose Level Abnormalities | Criteria: Blood glucose levels >15 milligram per deciliter (mg/dL) above ULN or >15 mg/dL below LLN. | Baseline up to 17 days after last dose of study drug (Day 31) | 
| Number of Participants With Hypoglycaemia | Hypoglycaemia is a condition characterized by abnormally low blood glucose (blood sugar) levels, usually <=50 mg/dL. | Baseline up to 17 days after last dose of study drug (Day 31) | 
| Number of Participants With Drug-Induced Liver Injury | Criteria for drug induced liver injury: Levels of aspartate transaminase (AST) or alanine transaminase (ALT) should be >= 3 times ULN concurrent with a total bilirubin of >=2 times ULN with no evidence of hemolysis and an alkaline phosphatase should be <=2 times ULN. | Baseline up to 17 days after last dose of study drug (Day 31) | 
| Change From Baseline in Predose Fasting Glucose Levels at Day 8 | Fasting glucose levels were determined before administration of OAP-189 using a glucometer. | Baseline, Day 8 | 
| Change From Baseline in Predose Fasting Glucose Levels at Day 15 | Fasting glucose levels were determined before administration of OAP-189 using a glucometer. | Baseline, Day 15 |