Clinical trial NCT01874366: Determination of Safety,Tolerability,Pharmacokinetics,Food Effect& Pharmacodynamics of Single & Multiple Doses of P11187
Official title: A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Safety, Tolerability, Pharmacokinetics, Food Effect and Pharmacodynamics of Single and Multiple Ascending Doses of P11187
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Overweight
Diabetes Mellitus Type 2 in Obese
Lead sponsor: Piramal Enterprises Limited
Sponsor class: INDUSTRY
Collaborators: name: Quintiles, Inc.
name: Miami Research Associates
First posted: 2013-06-11
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: * In Part I, the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of P11187 will be studied in healthy, overweight or obese, male and females (of non-child bearing potential) subjects. There will be up to 6 cohorts of 8 subjects each. At each dose level, 6 subjects will receive a single dose of active treatment, P11187 and 2 subjects will receive a single dose of matching placebo. It is planned that up to 6 dose levels of P11187 may be evaluated after single dose administration.
* In Part II, the safety, tolerability, PK and PD of multiple ascending doses of P11187 administered once daily for 14 consecutive days will be studied in overweight or obese, male and female of non-child bearing potential subjects with type 2 diabetes mellitus. Up to 3 dose levels of P11187 are planned to be evaluated in 3 cohorts of 12 subjects each for 14 days.At each dose level, 9 subjects will receive the active drug, P11187 and 3 subjects will receive matching placebo, once daily for a period of 14 days.
* In Part III, the food effect evaluation of P11187 will be performed in a randomized, open-label, cross-over, two-period study at a single dose level in a cohort of 12 healthy male subjects to be administered the drug under fasted and fed conditions.Subjects will be administered a single dose of P11187 in Periods 1 and 2 under fasted and fed conditions as per the randomization schedule, with a wash-out interval of 7-10 days between the two periods. Subjects who have received the study drug, P11187 under fasted conditions in Period 1 will cross-over and receive the study drug under fed conditions in Period 2 and vice versa.

Eligibility 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)

Primary outcomes:
measure: Number of participants with adverse events (single and multiple dose studies)
timeFrame: 12-14 Months
measure: Food Effect
timeFrame: 12-14 Months
Secondary outcomes:
measure: Change in Oral Glucose Tolerance Test (OGTT)
timeFrame: 12-14 month
measure: Area under the plasma concentration (AUC)
timeFrame: 12- 14 Month
measure: Change in Intravenous Glucose Tolerance Test
timeFrame: 12- 14 Month
measure: Change in the Mixed Meal Tolerance Test
timeFrame: 12- 14 Month
measure: Peak Plasma concentration (Cmax)
timeFrame: 12- 14 Month
measure: Time to peak plasma concentration (t-max)
timeFrame: 12- 14 Month
Other outcomes:
Locations:
city: Miami
country: United States
facility: Phase I clinic: MRA Clinical Research
state: Florida
Study officials:
affiliation: Phase I clinic: MRA Clinical Research
name: Patricia Pardo,, MD
role: PRINCIPAL_INVESTIGATOR
References: