A Phase 2A, Randomized, Placebo-controlled, Parallel group, Multiple-dose study to evaluate the Efficacy, Safety and Tolerability of 12-week oral administration of PF-00734200 tablets to subjects with Type 2 Diabetes Mellitus on stable treatment with Metformin - N/A

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-001922-28-SE
• Date of registration: 21/06/2007
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017
• Public title: A Phase 2A, Randomized, Placebo-controlled, Parallel group, Multiple-dose study to evaluate the Efficacy, Safety and Tolerability of 12-week oral administration of PF-00734200 tablets to subjects with Type 2 Diabetes Mellitus on stable treatment with Metformin - N/A
• Scientific title: A Phase 2A, Randomized, Placebo-controlled, Parallel group, Multiple-dose study to evaluate the Efficacy, Safety and Tolerability of 12-week oral administration of PF-00734200 tablets to subjects with Type 2 Diabetes Mellitus on stable treatment with Metformin - N/A
• Date of first enrolment: 07/08/2007
• Target sample size: 320
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-001922-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: yes Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany, Italy, Spain, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible for placebo run in period and enrollment into the double blind study:

4.1.1. Diagnosis of Type 2 Diabetes Mellitus per ADA

Subjects must be diagnosed with type 2 diabetes mellitus in accordance with the ADA guidelines. Diagnosis may have occurred in the recent past (documented patient medical history). Guidelines for diagnosis include at least one of the following criteria:
• Symptoms of diabetes in addition to casual plasma glucose concentration =200 mg/dl. Term ‘casual’ is defined as plasma glucose concentration at any time of day
without regard to time since last meal. The classic symptoms of diabetes include polyuria, polydipsia, and/or unexplained weight loss.
OR:
• FPG (fasting plasma glucose) =126 mg/dL. Term ‘fasting’ is defined as no caloric intake for at least 8 hours.
OR:
• Two hour post load glucose =200 mg/dL during an OGTT (oral glucose tolerance test). The test should be performed as described by WHO (World Health Organization), using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in ambient water.

4.1.2. Study Inclusion Criteria

1. Male and/or female subjects (non childbearing potential) between the ages of 18 and 70 years, inclusive.
2. Subjects currently taking a stable dose of metformin for treatment of their diabetes within past 2 months or longer before enrollment.
3. HbA1c >7% - 11% inclusive.
4. Fasting blood glucose levels in a range of =140 mg/dl to <270 mg /dL.
5. BMI =25 and =40 kg/m2, and a total body weight =50 kg (110 Lbs).
6. Documented evidence of obtained written and witnessed informed consent a subject (or their legal representative) signed and dated informed consent document in the presence of a witness.
7. Subjects are willing and able to comply with all study required procedures, including scheduled visits, assigned treatment, clinical laboratory tests.
8. Subjects are willing and able to perform self test of blood sugars twice daily.

4.1.3. Female Subjects of Non Childbearing Potential Inclusion Criteria

Female subjects of non childbearing potential must meet at least one of the following criteria:

Natural or surgically postmenopausal females, defined as:
• Natural postmenopausal females over the age of 60 years, (FSH >40mIU/mL)
• Natural postmenopausal females who are 45 to 60 years of age must be amenorrheic for at least 2 years and have a serum FSH (follicle stimulating hormone) level within the regional standard laboratory reference range for postmenopausal women and/or FSH >40mIU/mL.
• Surgically postmenopausal females who have undergone a total hysterectomy and/or total bilateral oophorectomy 6 months or earlier before the enrollment.
All other female subjects (including women who have undergone tubal ligations) will be considered as women of childbearing potential and will be excluded from participation in this study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects meeting any of the following criteria will be excluded from the study:

1. Recent (within 12 months of enrollment) evidence or medical history of unstable concurrent disease. For example, documented evidence or history of clinically significant hematological, renal, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding clinically insignificant drug allergies and untreated, asymptomatic, seasonal allergies).
2. Any medical condition possibly affecting study drug absorption (eg, gastrectomy).
3. A positive urine screen test for illegitimate/non prescribed use of commonly abused drugs.
4. Treatment with any class of investigational drug within 30 days preceding the screening.
5. Fasting serum triglycerides result =500 mg/dL.
6. Treatment with any oral hypoglycemic agent within 2 months before enrollment. The exception to these criteria is a stable dose of metformin for treatment of T2DM within the past 2 months or longer of enrollment.
7. History of repeated or frequent documented hypoglycemia over the last 6 months prior to enrollment.
8. Screening fasting blood glucose level <140 or >270 mg/dL.
9. Diagnosis of Type 1 diabetes mellitus.
10. Presence of positive glutamic acid decarboxylase (GAD) antibody titer.
11. Women of childbearing potential, pregnant or nursing.
12. The following therapeutic agents use is specifically not permitted:
Anticonvulsants, opioids, antiarrhythmics, coumarin type anticoagulants, antipsychotics, tricyclic and related antidepressants, and paroxetine. Corticosteroids, sympathomimetic agents, and over the counter omega 3 fatty acids are not permitted. Herbal supplements must be discontinued at least 28 days before the first double blind dose of study drug. Acetaminophen (paracetamol [EU]) allowed to be used at doses of =2 g per day.
13. Blood donation of approximately 1 pint (500 mL) within 56 days of enrollment.
14. History of sensitivity to heparin or heparin induced thrombocytopenia (including heparin use to flush intravenous catheters).
15. Evidence of diabetic complications with significant end organ damage, eg, proliferative retinopathy and/or macular edema, creatinine clearance =60 mL/min based on the Cockcroft Gault equation (listed below), diabetic neuropathy complicated by neuropathic ulcers.

Males: (140 – age in years) x total body weight (kg)/ 72 x serum creatinine (mg/dL)
Females: (0.85) x (Calculation for males)

16. Clinically significant peripheral vascular disease (eg, manifested by claudication).
17. History of stroke or transient ischemic attack.
18. Current medical history of unstable angina.
19. History of myocardial infarction within one year of enrollment.
20. 12 lead ECG at screening demonstrating QTc >450 msec.
21. Persistent severe uncontrolled hypertension, eg, supine systolic blood pressure (BP) =180 mm Hg and/or diastolic BP =105 mm Hg on at least 2 consecutive measurements following at least 10 minutes of rest between the measurements.
22. Any medical history or clinical evidence of congestive heart failure, NYHA (New York Heart Association) Functional Classification, Classes III IV.
23. Other severe acute and/or chronic medical and/or psychiatric conditions and/or abnormal laboratory test results that may increase the risk associated with study participation and/or investigational drug administration and/or may interfere with the interpretation of study results in the judgment

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Type 2 Diabetes Mellitus (T2DM)
MedDRA version: 9.1 Level: LLT Classification code 10012601 Term: Diabetes mellitus

Intervention(s)

Product Code: PF-00734200
Pharmaceutical Form: Tablet
Current Sponsor code: PF-00734200
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Code: PF-00734200
Pharmaceutical Form: Tablet
Current Sponsor code: PF-00734200
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: 1. To evaluate the effect of multiple oral doses of PF 00734200 tablet on change from baseline to 12 weeks of insulin AUC following mixed meal tolerance test (MMTT) in subjects with T2DM.
2. To evaluate the proportion of subjects achieving the current ADA glycemic goal of Hb A1c <7%.
3. To evaluate the safety and tolerability of multiple oral doses of PF 00734200 tablet administered to subjects with T2DM.

Main Objective: To compare the effect of multiple oral doses of PF 00734200 tablet versus placebo on change from baseline to 12 weeks of Hb A1c levels and evaluate dose response in subjects with T2DM on a stable dose of metformin.

The term ‘stable dose of metformin’ is defined as the same dose of metformin for at least 2 months prior to randomization.

Primary end point(s): • Assessment of Safety and Tolerability
Safety and tolerability will be assessed by physical examinations, adverse event monitoring, clinical safety laboratory tests, blood glucose level measured by glucometer, vital sign measurements, and 12 lead ECGs
• Assessment of PF 00734200 Pharmacokinetics
On Days 14, 56 and 84 fasting levels (0 hour) of PF 00734200.
On Day 84 fasting (0 hour) and 0.75, 1.75 and 3.25 hours post dose levels of PF 00734200.
• Assessment of Pharmacodynamics
The primary pharmacodynamic evaluative endpoint is HbA1c level.
A secondary pharmacodynamic evaluative endpoint is AUC of glucose and insulin following mixed meal tolerance test on Days 1 and 84 (or premature discontinuation).

Secondary ID(s)

A7941005

N/A