Study Evaluating Safety, Tolerability, And Action Of OAP-189 In Subjects With Type 2 Diabetes On Metformin (3283K1-1008-US)

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.

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: OAP-189; Drug: placebo comparator

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • Profil Institute for Clincal Research
  • Florida
    • Miami Gardens, Florida, United States, 33169
      • Cetero Research - Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2	Drug: placebo comparator; 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
Placebo Comparator: OAP-189	Drug: OAP-189; 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)

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration Versus Time Summary of Metformin Following Single Dose of OAP-189	Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLOQ =2 nanogram per millliter) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) =0.	Pre-dose (2 hours before dosing), 1, 2, 3, 4, 6 hours post-dose on Day 14
Plasma Concentration Versus Time Summary of Metformin Following Multiple Dose of OAP-189	Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLOQ =2 nanogram per millliter) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) =0.	Pre-dose (2 hours before dosing), 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24 hours post-dose on Day 7
Plasma Concentration Versus Time Summary of Single Dose of OAP-189	Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLOQ = 0.500 nanogram per millliter) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) =0.	Pre-dose (2 hours before dosing), 2, 4, 6 hours post-dose on Day 7; Pre-dose (2 hours before dosing), 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 48, 72 hours post-dose on Day 14
Plasma Concentration Versus Time Summary of Multiple Dose of OAP-189	Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLOQ =0.500 nanogram per millliter) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) =0.	Pre-dose (2 hours before dosing), 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24 hours post-dose on Day 7

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2009
• Primary Completion (Actual): July 25, 2011
• Study Completion (Actual): July 25, 2011

Study Registration Dates

• First Submitted: September 1, 2009
• First Submitted That Met QC Criteria: September 1, 2009
• First Posted (Estimate): September 2, 2009

Study Record Updates

• Last Update Posted (Actual): November 2, 2020
• Last Update Submitted That Met QC Criteria: October 28, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: 3283K1-1008; B2201004 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.