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

NCT01874366 | Unknown Phase 1

• 1 other identifier: P11187/77/13
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Overweight; Diabetes Mellitus Type 2 in Obese

Outcome Measures

Primary Outcomes (2)

• Number of participants with adverse events (single and multiple dose studies)

  * The safety and tolerability of single ascending doses of P11187 in healthy, overweight and/or obese, male and non-child bearing female subjects (Part I). * The safety and tolerability of multiple ascending doses of P11187 in overweight and/or obese, male and non-child bearing female subjects with type 2 diabetes mellitus (Part II).

  12-14 Months

• Food Effect

  The effect of food on the pharmacokinetics (PK) of P11187 following single oral doses in healthy male subjects, under fed and fasted conditions (Part III).

  12-14 Months

Secondary Outcomes (6)

• Change in Oral Glucose Tolerance Test (OGTT)

  12-14 month

• Area under the plasma concentration (AUC)

  12- 14 Month

• Change in Intravenous Glucose Tolerance Test

  12- 14 Month

• Change in the Mixed Meal Tolerance Test

  12- 14 Month

• Peak Plasma concentration (Cmax)

  12- 14 Month

Study Arms (2)

P11187

EXPERIMENTAL

* Part I: Step wise dose escalation in subsequent cohorts and will be based upon the review of safety and tolerability results of the preceding cohort * Part II: Step wise dose escalation in the multiple dosing for 14 consecutive days after review of the safety and tolerability of the preceding cohorts * Part III: Study drug will be administered under the fasted or fed conditions in two different periods separated by a wash-out interval of 7-10 days

Drug: P11187

Placebo

PLACEBO COMPARATOR

Placebo capsules will be matching in appearance with the active drug capsules of P11187.

Drug: Placebo

Interventions

P11187 DRUG

* Part I: Step wise dose escalation(10 to 1500 mg, qd, Oral) * Part II: Step wise dose escalation in multiple dosing (≤ 1500 mg, qd, Oral) for 14 consecutive days. * Part III: Study drug administered (≤ 1500 mg, qd, Oral) under fasted or fed conditions in two different periods separated by a wash-out interval.

Also known as: Oral G-Protein Coupled Receptor 40(GPR40)agonist

P11187

Placebo DRUG

Placebo capsules will be matching in appearance with the active drug capsules of P11187. * In Part I, there will be up to 6 cohorts of 8 subjects each in single dose assessment. Two subjects from each cohort will be dosed with placebo * In Part II, there will be 3 cohorts of 12 subjects each and three subjects from each cohort will be dosed with placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects willing to give written informed consent to participate in the study
• Male \& female subjects aged between 18 \&70 years (both inclusive) in Part I \& II) \& between 18 \&70 years (both inclusive) in Part III
• 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)
• Healthy subjects having no clinically significant abnormalities in medical history, physical examination, clinical laboratory tests, vital signs \& 12-lead electrocardiograms (ECG)
• Female subjects of non-child-bearing potential, post-menopausal or surgically sterilized (Part I \& II)
• Male subjects agreed to use contraceptive methods as per protocol during \& approximately 30 days after the exit/completion of their participation in the study
• Part II: Subjects with type 2 diabetes mellitus at least 6 mths prior to screening
• 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.
• Part II-Subjects with HbA1c between 6 \&11% at screening
• Part II-Subjects with fasting plasma glucose of ≤ 14.42 mmol/L (\~260 mg/dL) at screening
• Part II-Subjects with C-peptide value of \> 0.266 nmol/L (0.8 ng/mL) at screening

You may not qualify if:

• Subjects with history of (H/O) significant gastrointestinal, cardiac, renal or liver impairment
• Subjects with known congenital QTc prolongation or QTcF greater than 450 ms
• 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
• Subjects with H/O anaphylaxis/angioedema, adult bronchial asthma, peptic ulcer \& clinically important food/drug allergy
• Subjects with H/O drug abuse/addiction/use of recreational drugs ,mental handicap, psychiatric disorders including eating disorders/seizures /significant head trauma
• 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
• Subjects with prior exposure to P11187/ have participated in previous cohorts or have participated in another clinical trial 30 days prior to screening
• 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.
• 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.
• 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
• Part II-Subjects with H/O heart failure (NYHA class III \&IV)/myocardial infarction/unstable angina /cerebrovascular accident
• Part II-Subjects with severe/uncontrolled hypertension(above 160/100 mm Hg)

Sponsors & Collaborators

• Piramal Enterprises Limited: lead
• Quintiles, Inc.: collaborator
• Miami Research Associates: collaborator

Study Sites (1)

Phase I clinic: MRA Clinical Research

Miami, Florida, 33143, United States

RECRUITING

MeSH Terms

Conditions

Overweight

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Patricia Pardo,, MD

  Phase I clinic: MRA Clinical Research

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr. Alan Hatfield, MD

CONTACT

+91 22 3027 5002; alan.hatfield@piramal.com

Dr. Purvi Chawla, MS

CONTACT

+91 22 3027 5127; purvi.chawla@piramal.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2013
• First Posted: June 11, 2013
• Study Start: June 1, 2013
• Primary Completion: October 1, 2015
• Study Completion: December 1, 2015
• Last Updated: August 28, 2014

Record last verified: 2014-08

Locations

US (1)