Determination of Safety,Tolerability,Pharmacokinetics,Food Effect& Pharmacodynamics of Single & Multiple Doses of P11187

• Status: Unknown status
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: All

Summary

• Study to Determine the Safety, Tolerability, Pharmacokinetics, Food Effect and Pharmacodynamics of Single and Multiple Ascending Doses of P11187

• It will be conducted in three parts, as described below:

• Part I will be the Single Ascending Dose (SAD) study

• Part II will be the Multiple Ascending Dose (MAD) study

• Part III will be the food effect evaluation

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Piramal Enterprises Limited
• Collaborators: Miami Research Associates; Quintiles, Inc.

Criteria

Inclusion Criteria:

1. Subjects willing to give written informed consent to participate in the study

2. Male & female subjects aged between 18 &70 years (both inclusive) in Part I & II) & between 18 &70 years (both inclusive) in Part III

3. Subjects with a body mass index (BMI) between 19 &42 kg/m2(Part I), 22 &42 kg/m2 (Part II) & 19 &27 kg/m2 (Part III)

4. Healthy subjects having no clinically significant abnormalities in medical history, physical examination, clinical laboratory tests, vital signs & 12-lead electrocardiograms (ECG)

5. Female subjects of non-child-bearing potential, post-menopausal or surgically sterilized (Part I & II)

6. Male subjects agreed to use contraceptive methods as per protocol during & approximately 30 days after the exit/completion of their participation in the study

7. Part II: Subjects with type 2 diabetes mellitus at least 6 mths prior to screening

8. Part II: Subjects on diet & exercise alone or on a stable dose of metformin for a period of at least 2 mths before screening. Subjects who are washed off other medications such as sulfonyureas /alpha-glucosidase inhibitors, at least 14 days prior to dosing.

9. Part II-Subjects with HbA1c between 6 &11% at screening

10. Part II-Subjects with fasting plasma glucose of ≤ 14.42 mmol/L (~260 mg/dL) at screening

11. Part II-Subjects with C-peptide value of > 0.266 nmol/L (0.8 ng/mL) at screening

Exclusion Criteria:

1. Subjects with history of (H/O) significant gastrointestinal, cardiac, renal or liver impairment

2. Subjects with known congenital QTc prolongation or QTcF greater than 450 ms

3. Subjects with H/O hypo/hyperthyroidism (except replacement with thyroxine & on a stable dose since the past 2 mths), repeated thyroid stimulating hormone (TSH) values that is abnormal at screening or subjects with a H/O obesity of endocrine origin

4. Subjects with H/O anaphylaxis/angioedema, adult bronchial asthma, peptic ulcer & clinically important food/drug allergy

5. Subjects with H/O drug abuse/addiction/use of recreational drugs ,mental handicap, psychiatric disorders including eating disorders/seizures /significant head trauma

6. Subjects with H/O alcoholism for more than 2 years /consumption of more than 3 alcoholic drinks per day/consumption of alcohol, 2 days prior to confinement/ during the study

7. Subjects with prior exposure to P11187/ have participated in previous cohorts or have participated in another clinical trial 30 days prior to screening

8. Subjects undergone weight-loss surgery/ consuming prescription drugs including sedatives &steroids within 30 days before first drug administration/ using over-the-counter drugs including herbal/ health supplements & others such as St. John's Wort extract . Subjects consumed weight loss medications within 90 days before the first drug administration.

9. Part II- Subjects with using insulin within 6 mths prior to screening except when used for short duration (less than 14 days) or was being treated with GLP-1 analogues / other anti-diabetic medications except metformin within 6 mths prior to screening. Subjects being treated with herbal/OTC drugs including sulfonylureas/alpha-glucosidase inhibitors unless discontinued/washed-out at least 14 days prior to dosing.Subjects on anti-hypertensive &lipid-lowering medications (only statins) will only be allowed if they are at the same dose since the past 2 mths & are maintained at the same dose throughout the study duration.

10. Part II-Subjects with H/O metabolic complications, mature Onset Diabetes of the Young (MODY)/insulin-dependent type 2 diabetes mellitus/ other unusual forms of diabetes mellitus. Subjects with known endocrine disorders

11. Part II-Subjects with H/O heart failure (NYHA class III &IV)/myocardial infarction/unstable angina /cerebrovascular accident

12. Part II-Subjects with severe/uncontrolled hypertension(above 160/100 mm Hg)