| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10029883 |
| E.1.2 | Term | Obesity |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| Determine in overweight/obese subjects with type 2 diabetes mellitus whether body weight can be made significantly lower by treatment with CP 945,598 compared to treatment with placebo. |
|
| E.2.2 | Secondary objectives of the trial |
• Determine in overweight/obese subjects with DM type 2 on MET or SU monotherapy whether HbA1c can be significantly lowered by treatment with CP 945,598 compared to placebo;
• Effect of CP 945,598 at 1 year on:
• Proportion of subjects who lose 5% and 10% body weight;
• Proportion of subjects with HbA1c < 6.5;
• Proportion of subjects with HbA1c < 7.0;
• Change from BL waist circumference;
• Change from BL fasting TG and HDL concentrations;
• Effect of CP-945,598 on Changes in PRO Scales at 1 year:
• Uncontrolled Eating
• Power of Food
Exploratory Objectives:
• Safety and tolerability of CP-945,598;
• Effect of CP-945,598 on sevreral parameters not listed above:
• pharmacokinetics;
• PK/PD relationship between CP-945,598 and changes in indices
of glycemic control, body weight; |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Sub-Study Only: Oral Glucose Tolerance Test (OGTT), amendment 3, 31 May 2007
- Explore the effect of CP-945,598 on fasting and postprandial insulin concentrations determined from OGTT in subset of subjects
Sub-Study Only: 7-Point Home Glucose Monitoring, amendment 3, 31 May 2007
- Explore the effect of CP-945,598 on 7-Point Home Glucose Profiles in a subset of subjects
|
|
| E.3 | Principal inclusion criteria |
1. Male and/or female subjects 18-70 years of age, inclusive, with BMI 27-50 kg/m2
inclusive, and with type 2 diabetes mellitus as defined by the American Diabetes
Association for at least 4 months.
2. Subjects on stable oral anti diabetes regimens (no changes in agents or doses for
at least 4 months) consisting of sulfonylurea (SU - any locally approved sufonyl-
urea), metformin (Met), thiazolidinedione (TZD - rosiglitazone or pioglitazone),
sitagliptin, meglitinides (MEG - repaglinide or nateglinide), or alpha-glucosidase
inhibitors (AGI - acarbose or miglitol). These agents may be used as monotherapy
or in combinations found in the table in protocol. Each background diabetes
medication should be taken at maximally allowable doses per prescribing
information or taken at doses which are adequate for study participation in the
judgement of the investigator. Note: Doses of background diabetes medication
may not be changed during the course of the study except in specific
circumstances (see Section 6.1 for diabetes management details). For combination
medication, each component of the combined tablet must satisfy the above
criteria.
3. Screening HbA1c between 6.5% and 10%, inclusive.
4. Week 1 fasting plasma glucose NMT 270 mg/dl (15 mmol/L).
5. Subjects must have documentation of an appropriate ophthalmologic exam
(including dilated examination of the fundus) by a qualified health care
professional, during the 12 months prior to randomization.
6. For women of childbearing potential, a negative serum pregnancy test will be
required prior to study inclusion. Female subjects must be surgically sterile or be
postmenopausal or must agree to use effective contraception during the study.
For the UK only, acceptable methods of contrazeption are found in Section 4.3.2.1.
For all other countries, the definition of effective contraception will be based on
the judgement of the Investigator or a designated associate. Oral contraceptive
use is permitted if used for at least 3 months before starting study medication.
7. Evidence of a personally signed and dated informed consent document indicating
that the subject (or a legally acceptable representative) has been informed of all
pertinent aspects of the trial.
8. Subjects who are able to comply with scheduled visits, treatment plan (including
diet and exercise program), home blood glucose monitoring, laboratory tests, and
other trial procedures.
|
|
| E.4 | Principal exclusion criteria |
1.Women who are pregnant or lactating, or who are actively planning to become
pregnant.
2.Subjects with clinically significant abnormalities identified during the screening
process. Specific exclusions include:
a.Subjects with blood pressure reading of systolic BP >155 mmHg and/or diastolic
BP >95 mmHg (confirmed by repeat measurement at the screening visit ) or
requiring new pharmacologic treatment or change in current treatment according
to local guidelines for diabetic patients;
b.Subjects with clinically significant cardiovascular disease, defined as unstable
coronary heart disease (CHD), cerebrovascular disease (CVD) or peripheral
vascular disease (PVD) and/or an event/intervention during the past 6 months;
Note: Clinically stable subjects with a history of CHD, CVD or PVD, provided that the level of exercise proposed in the trial is deemed safe and appropriate for the subject may be included.
c.Subjects with dyslipidemia requiring new pharmacological treatment or a change in
current treatment according to local guidelines for diabetic patients;
d.Subjects with renal disease including:
•Any history of nephrotic syndrome,
•Chronic renal failure and/or serum creatinine above the upper limit of normal (ULN)
for metformin-treated patients or >1.5 times the ULN for patients not treated with
metformin.
e.Subjects with abnormal screening TSH values;
f.Subjects with significant hepatobiliary disease including:
•History of hepatitis B or C infection and/or,
•Aspartate aminotransferase or alanine aminotransferase NLT 2 times the ULN.
g.History of HIV infection or use of antiretroviral agents;
h.Subjects with any prior history of malignancy except for:
•Basal cell carcinoma of the skin curatively treated,
•Other malignancies (regardless of site) that have been cancer-free for 5 years
prior to screening.
i.Subjects with gastrointestinal disease, surgery limiting drug absorption or previous
history of surgical procedure for weight loss;
j.Clinical laboratory tests outside the pre-specified exclusionary limits;
k.Subjects with a history of CNS disorder including:
•A mood disturbance that meets the criteria for a Major Depressive Disorder within
the last 10 years prior to screening, defined as requiring hospitalization, two or
more episodes of a major depressive disorder or any previous suicide attempt;
•Use of antidepressants that are known to increase weight;
Note: Subjects on a maintenance dose of other permitted antidepressants for a major depressive disorder, stable and in remission for at least 3 months prior to screening, and who plan to continue this treatment during the entire trial may be included.
•Subjects with a score of NLT 10 or who score positively on the item 9 addressing
suicidal ideas on the PHQ-9;
•Subjects with psychotic conditions or on antipsychotic pharmacotherapy;
•Subjects with seizure disorders who:
1.Are not controlled by current antiepileptic treatment, and/or
2.Are taking antiepileptic drugs (AEDs) known to affect weight positively or
negatively unless these medications have been taken at a stable dose for at
least 6 months and the subject’s weight has been stable over the same time
period, and/or
•That may increase the risk of a drug-drug interaction.
•Subjects with neurological disorders that are acute, chronic relapsing, progressive
or have an unpredictable course.
3.Subjects who use marijuana (determined by medical history).
4.Subjects who frequently change smoking habits or have stopped smoking within 6
months prior to screening.
5.Subjects with known history of alcoholism or drug abuse or dependence within 1
year prior to screening.
6.Subjects with a history of anorexia, bulimia nervosa or binge eating disorder as
per DSM-IV TR.
7.Use of prescription drugs or over the counter agents/supplements known to alter
body weight or appetite within 3 months prior to screening.
8.Systemic therapy with strong CYP3A inhibitors.
9.Systemic therapy with clinically significant CYP3A inducers or regular consumption
of grapefruit/grapefruit juice.
10.Treatment with any anti-diabetic agent within the last 4 months not allowed in
inclusion criterion # 2.
11.Treatment with an investigational drug during the 30 days prior to screening.
12.Participation in any formal weight loss program within 3 months prior to screening.
13.Fluctuation in body weight >5% within 3 months prior to screening.
14.Failure to satisfactorily complete at least 5 of the 7-day food intake and
physical activity records.
15.Subjects with any other medical condition or laboratory abnormality prior to
randomization, which in the opinion of the investigator or sponsor could affect
subject safety, preclude evaluation of response, or render unlikely that the
subject would complete the study.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Percent change in body weight from baseline (Day 1) to 1 year |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Patient Reported Outcomes |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 25 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
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