E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Obesity and mixed dyslipidemia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029883 |
E.1.2 | Term | Obesity |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058110 |
E.1.2 | Term | Dyslipidemia |
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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 |
The co-primary objectives of the study are 1) to evaluate the potential efficacy and dose response of LCQ908 as a therapy for the treatment of obesity (weight loss) and 2) To evaluate the potential efficacy and dose response of LCQ908 as a treatment for the dyslipidemia (LDL-cholesterol) associated with the metabolic syndrome. The trial will be declared positive if either one or both primary endpoints are met. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to evaluate the effects of LCQ908 on weight loss status (≥ 5%, or < 5%), changes in waist circumference, insulin sensitivity, and specific elements of the lipid profile including chylomicron remnants and HDL subtypes. Additional objectives are to evaluate the effect on other features of the metabolic syndrome including blood pressure and markers of inflammation. Finally, an MRI substudy of the effect of LCQ908 on hepatic fat fraction (HFF) will provide pilot data regarding other potential therapeutic benefits in patients with non-alcoholic fatty liver disease (NALFD) or non-alcoholic steatohepatitis (NASH). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Written informed consent to participate in the study, before any study related activities are performed, and is likely to comply with all study requirements, including dietary guidelines. 2.Age 18-75 years, inclusive. 3.Males, non-fertile females, and females of non-childbearing potential. Women must be (a) postmenopausal, defined as age >48 with 12 months of natural (i.e. spontaneous) amenorrhea or age >42 with >6 months of spontaneous amenorrhea with serum FSH levels > 30 mIU/mL and estradiol <30 pg/ml ; (b) 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy; or (c) have a documented history of tubal ligation at least 1 year prior to screening. 4.Patients with a history of overweight for 1 year or more with body mass index (BMI) of 30 to 42 kg/m2 inclusive. 5.Body weight at Visit 1 within 5% of their self-reported weight over the past three months and agreement to maintain the study-recommended diet (counseled during screening) and usual exercise habits during the full course of the study. Patients will not have participated in a formal weight loss program within the 3 months prior to screening Visit 1. 6.Patients with fasting mixed dyslipidemia at the first screening visit including: - elevated LDL cholesterol of 2.6 to 4.14 mmol/L (100-160 mg/dl) inclusive and either - fasting triglycerides of 1.7 to 5.0 mmol/L (150-520 mg/dl) inclusive or - HDL cholesterol in men <1.1 mmol/L (<42 mg/dl) and in women <1.3 mmol/L (<50 mg/dl) 7.Patients who are receiving a statin must meet the dyslipidemia criteria while on their statin and must have been on a stable dose for at least 2 months prior to the Visit 1 fasting lipids and safety screening. They must agree to maintain the same dose of statin throughout the trial duration. 8.Patients who have not been on fibrate or nicotinic (niacin) lipid lowering therapies within 2 months of Visit 1 are eligible for screening so long as they meet all other criteria. Patients on over-the-counter fish oils, prescription fish oils (Lovaza up to 4 g/day) or other natural product approaches to lipid lowering may remain on those as long as they meet other entry criteria. |
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E.4 | Principal exclusion criteria |
1.A history of type 1 diabetes or diagnosed type 2 diabetes, or other forms of diabetes mellitus. Women with a history of gestational diabetes occurring 5 or more years prior to screening are eligible if they meet the other metabolic criteria 2.Fasting plasma glucose > 7.0 mmol/L (>126 mg/dl) or HgbA1c >6.5 % 3.Known endocrine disorders that result in obesity including hypothalamic disorders, Cushing’s disease or recently diagnosed (within the prior 6 months) hypothyroidism 4.Genetic obesity syndromes, including Prader-Willi Syndrome 5.Dyslipidemia syndromes that require nicotinic acid or fibrates for control or need for accelerated treatment, including Triglycerides >5.0 mmol/L (520 mg/dl) and LDL cholesterol > 4.14 nmol (160 mg/dl) 6.Patients with known Type I or Type V chylomicronemia 7.For patients considered for the MRI sub-study: claustrophobia, waist circumference exceeding the bore size of the MRI scanner, and presence of ferromagnetic implants such as older pacemakers |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is the change from baseline of HbA1c at 12 weeks (or the last available post-randomization value). |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 21 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 21 |