OverweightPhase 1NCT01874366
Determination of Safety,Tolerability,Pharmacokinetics,Food Effect& Pharmacodynamics of Single & Multiple Doses of P11187
A Phase 1 study testing P11187 in people with Overweight and Diabetes Mellitus Type 2 in Obese, run by Piramal Enterprises Limited at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Overweight, Diabetes Mellitus Type 2 in Obese
- What is being tested?
- P11187
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2013to Dec 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Phase I clinic: MRA Clinical Research
Miami, Florida, 33143
Patricia Pardo, MD, 305-722-0970 ext. 5110, ppardo@miamiresearch.com
About this study
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 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
Read the 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.
- Conditions
- Overweight, Diabetes Mellitus Type 2 in Obese
- Being tested
- P11187, Placebo
- Medical subject headings
- Overweight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
P11187Drug
Also called Oral G-Protein Coupled Receptor 40(GPR40)agonist
- 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.
PlaceboDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: P11187 |
| Placebo | Placebo comparator | Placebo capsules will be matching in appearance with the active drug capsules of P11187. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 12-14 Months
Secondary outcomes (6)
Change in Oral Glucose Tolerance Test (OGTT)
To determine the effect of single doses of P11187 on pharmacodynamic (PD) parameters (Part I) in the study population defined as follows:
- Change in Oral Glucose Tolerance Test (OGTT) variables such as glucose AUC, insulin AUC, C-peptide AUC, glucagon AUC, GLP-1 AUC and GIP AUC.
Measured: 12-14 month
Area under the plasma concentration (AUC)
- To characterize the pharmacokinetics of P11187 following single and multiple doses (Part I and Part II) in the study population as defined.
- A non-compartmental PK method will be used to analyze the plasma levels of P11187 on Days 1 (Part I, II \& III) and Day 14 (Part II)
- The PK profile will be derived from the P11187 plasma concentration data in both periods i.e. fasted and fed states (Part III).
Measured: 12- 14 Month
Change in Intravenous Glucose Tolerance Test
- Multiple doses of P11187 on pharmacodynamic (PD) parameters (Part II) in the study population defined as follows:
- Change in Intravenous Glucose Tolerance Test (IVGTT) variables including glucose , insulin and C-peptide will be measured following an IVGTT.
Measured: 12- 14 Month
Change in the Mixed Meal Tolerance Test
- To determine the effect of multiple doses of P11187 on pharmacodynamic (PD) parameters (Part II) in the study population defined as follows:
- Change in the Mixed Meal Tolerance Test (MMTT) variables such as glucose , insulin, C-peptide, glucagon, GLP-1 and GIP.
Measured: 12- 14 Month
Peak Plasma concentration (Cmax)
- To characterize the pharmacokinetics of P11187 following single and multiple doses (Part I and Part II) in the study population as defined.
- A non-compartmental PK method will be used to analyze the plasma levels of P11187 on Days 1 (Part I, II \& III) and Day 14 (Part II)
- The PK profile will be derived from the P11187 plasma concentration data in both periods i.e. fasted and fed states (Part III).
Measured: 12- 14 Month
Time to peak plasma concentration (t-max)
- To characterize the pharmacokinetics of P11187 following single and multiple doses (Part I and Part II) in the study population as defined.
- A non-compartmental PK method will be used to analyze the plasma levels of P11187 on Days 1 (Part I, II \& III) and Day 14 (Part II)
- The PK profile will be derived from the P11187 plasma concentration data in both periods i.e. fasted and fed states (Part III).
Measured: 12- 14 Month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2013 (estimated)
- Study startJun 2013
- Primary completionOct 2015 (estimated)
- Study completionDec 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OverweightStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Piramal Enterprises Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Quintiles, Inc., Miami Research Associates
- Responsible party
- Sponsor
- Investigators
- Patricia Pardo,, MD, Principal investigator, Phase I clinic: MRA Clinical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01874366
- Sponsor's protocol ID
- P11187/77/13
- Status last verified
- Aug 2014
- First submitted
- 17 May 2013
- Last updated
- 28 Aug 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01874366
- Acronym / sponsor ID
- P11187/77/13
- Conditions
- Overweight, Diabetes Mellitus Type 2 in Obese
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- Piramal Enterprises LimitedIndustry (pharma, biotech, devices)
- Collaborators
- Quintiles, Inc., Miami Research Associates
- Study start
- Jun 2013
- Primary completion
- Oct 2015 (estimated)
- Study completion
- Dec 2015 (estimated)
- First posted
- 11 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| P11187 | Experimental | Drug: P11187* 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 |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo capsules will be matching in appearance with the active drug capsules of P11187. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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)
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| P11187Also: Oral G-Protein Coupled Receptor 40(GPR40)agonist* 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. | Drug | P11187 |
| PlaceboPlacebo 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 | Drug | Placebo |
Primary outcome
Number of participants with adverse events (single and multiple dose studies)
Time frame: 12-14 Months
* 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).
Food Effect
Time frame: 12-14 Months
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).
6 secondary outcomes
Change in Oral Glucose Tolerance Test (OGTT)
Time frame: 12-14 month
Area under the plasma concentration (AUC)
Time frame: 12- 14 Month
Change in Intravenous Glucose Tolerance Test
Time frame: 12- 14 Month
Change in the Mixed Meal Tolerance Test
Time frame: 12- 14 Month
Peak Plasma concentration (Cmax)
Time frame: 12- 14 Month
Time to peak plasma concentration (t-max)
Time frame: 12- 14 Month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patricia Pardo,, MD principal investigator
Phase I clinic: MRA Clinical Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing P11187 in people with Overweight and Diabetes Mellitus Type 2 in Obese, run by Piramal Enterprises Limited at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dr. Alan Hatfield, MD (+91 22 3027 5002 ext. 5002, alan.hatfield@piramal.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events (single and multiple dose studies) (time frame: 12-14 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2014.