|E.1 Medical condition or disease under investigation
|E.1.1||Medical condition(s) being investigated ||
|E.1.2 Medical condition or disease under investigation
|E.1.2||Classification code ||10029883
|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 the long term efficacy of CP-945,598 on body weight in obese subjects or
overweight subjects with co-morbid conditions after 1 and 2 years of dosing.
|E.2.2||Secondary objectives of the trial ||
|• Evaluate the safety and tolerability of CP-945,598 in a 2-year outpatient setting.
• Explore the effect of CP-945,598 on:
• Proportion of subjects who lose 5 and 10% body weight during the first and
• Proportion of subjects maintaining 80% weight loss during the second year,
• Waist circumference,
• Pharmacodynamic measurements including glucose, insulin, total cholesterol,
LDL-C, HDL-C, triglycerides, apolipoprotein AI (Apo-AI), apolipoprotein
B (Apo-B), number and size of LDL particles, adiponectin, and hsCRP,
• Prevalence of metabolic syndrome,
• Patient Reported Outcomes,
• Characterize the pharmacokinetics of CP-945,598 in the target population including
an assessment of covariate effects by population PK modeling.
• Explore PK/PD relationships between CP-945,598 exposure and changes in body
weight, and other selected secondary endpoints as permitted by the data.
|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||
|Clinical Pharmacogenomics Supplement of a 2-year, randomized, double-blind, placebo-controlled phase 3 study to evaluate the long-term efficacy and safety of CP-945, 598 in the treatment of obese subjects.
Objective : investigate possible associations between genomic variation in relation to response to CP-945, 598 and in relation to characteristics of obesity and related conditions. Scientific information about these differences among groups of subjects can help researches to better understand the response of subjects to investigational drugs such as CP-945, 598 and to learn more about conditions such as obesity.
|E.3||Principal inclusion criteria ||
|1. Male and/or female subjects between 18 and 70 years of age inclusive.
2. 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. Oral contraceptive use is permitted if used for at least 3 months before starting study medication.
3. Male subjects must be surgically sterile or must use effective contraception during the study.
Note: The definition of effective contraception for both women and men will be based on the judgment of the Investigator or a designated associate.
4. Body Mass Index (BMI) ≥30 kg/m2, for subjects without co-morbidities; ≥27 kg/m2 for subjects with co-morbidities (treated or untreated hypertension and/or treated or untreated dyslipidemia):
A. Hypertension is defined as:
a. Systolic BP ≥140 and/or diastolic BP ≥90 mm Hg and/or,
b. On anti-hypertensive medication.
B. Dyslipidemia is defined as:
a. LDL-C not at goal according to local guidelines and/or,
b. Triglycerides ≥150 mg/dL and/or,
c. HDL-C <40 mg/dL and/or,
d. On any anti-dyslipidemic medication.
Note: Treated subjects for hypertension and/or dyslipidemia should have been on
stable therapy for at least 2 months prior to screening.
5. 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.
6. Subjects who are willing and able to comply with scheduled visits, treatment plan,
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
2.Subjects with clinically significant abnormalities identified during the screening
process. Specific exclusions include the following:
a.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.
b.Subjects with systolic BP ≥160 and/or diastolic BP ≥100 mm Hg or requiring new
pharmacological treatment or change in current treatment according to local
c.Subjects with dyslipidemia requiring new pharmacological treatment or change in
current treatment according to local guidelines.
d.Subjects with diabetes or fasting blood glucose concentration ≥126 mg/dL.
e.Subjects with renal disease including:
•Any history of nephrotic syndrome
•Chronic renal failure and/or serum creatinine >1.5 times the upper limit of normal
f.Subjects with abnormal screening TSH values.
g.Subjects with significant hepatobiliary disease including:
•History of hepatitis B or C infection and/or
•Aspartate aminotransferase or alanine aminotransferase ≥2 times the ULN.
h.History of HIV infection or use of anti-retroviral agents.
i.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 greater
than 5 years prior to screening.
j.Subjects with gastrointestinal disease, surgery limiting drug absorption or previous
history of surgical procedure for weight loss.
k.Clinical laboratory tests outside the pre-specified exclusionary limits.
l.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 a permitted antidepressant 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 ≥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,
2.Are taking antiepileptic drugs (AEDs) known to affect weight positively (eg,
valproic acid) or negatively (eg, topiramate, zonisamide) 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.
•Subjects with neurological disorders that are acute, chronic relapsing, progressive
or have an unpredictable course.
3.Subjects who frequently change smoking habits or have stopped smoking within 6
months prior to screening.
4.Subjects who use marijuana (determined by medical history).
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.Participation in any formal weight loss program within the 3 months prior to
8.Fluctuation in body weight >5% within 3 months prior to screening.
9.Failure to satisfactorily complete at least 5 of the 7-day food intake and/or physical
10.Use of prescription drugs or over the counter agents/supplements known to alter
body weight or appetite within 3 months prior to screening.
11.Systemic therapy with strong CYP3A inhibitors.
12.Systemic therapy with clinically significant CYP3A inducers or regular consumption
of grapefruit/grapefruit juice.
13.Treatment with an investigational drug during the 30 days prior to screening.
14.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 end of 1 year and year 2
|E.6 and E.7 Scope of the trial
|E.6||Scope of the trial
|E.6.1||Diagnosis|| Information not present in EudraCT
|E.6.2||Prophylaxis|| Information not present in EudraCT
|E.6.3||Therapy|| Information not present in EudraCT
|E.6.8||Bioequivalence|| Information not present in EudraCT
|E.6.9||Dose response|| Information not present in EudraCT
|E.6.10||Pharmacogenetic|| Information not present in EudraCT
|E.6.12||Pharmacoeconomic|| Information not present in EudraCT
|E.6.13||Others|| Information not present in EudraCT
|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.188.8.131.52||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.8.1.3||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.8.2|| Comparator of controlled trial
|E.8.2.1||Other medicinal product(s)|| No
|E.8.2.2||Placebo || Yes
The trial involves single site in the Member State concerned
|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||7
|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
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||11
|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||11