Influence of Carboxypeptidase D (CPD) Gene on Body Weight and Fat Mass Reduction by Perindopril in Obese Subjects

• Status: Terminated
• Trial end date: 2017-04-27
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to evaluate the Carboxipeptidase D (CPD) genotyping as a predictive biomarker of body weight and/or fat mass reduction in obese patients treated with perindopril.

There is nonclinical and clinical evidence that a subgroup of human subjects may present a decrease in body weight and/or fat mass following treatment with perindopril. Although the individual characteristics that determine such effect are still unknown, Gene PreDiT SA (Biocant Park, Cantanhede, Portugal) discovered that certain genetic characteristics (e.g., single nucleotide polymorphisms (SNPs) of CPD gene) may play a role and potentially could serve as a potential predictive biomarker of response to perindopril.

These promising results, along with the fact that perindopril is a medicine already in use in clinical practice, led Gene PreDiT SA to decide to proceed with the development of a theranostic approach for the treatment of obesity. Such theranostic approach consists on the use of CPD genotyping to identify obese subjects that could present improved body weight and fat mass reduction following treatment with perindopril.

The current clinical trial aims to prove the concept and provide data to design further confirmatory studies. Additionally this study will evaluate the association between CPD SNPs genotypes and response to perindopril; the effect of perindopril in waist circumference, waist/hip ratio, and BMI and the tolerability and safety of perindopril in the study population.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gene PreDiT
• Collaborators: Blueclinical Ltd; Blueclinical, Ltd.
• Treatments: Perindopril

Criteria

Inclusion Criteria:

• Written informed consent;

• Man or woman with 18 years or more;

• Body Mass Index (BMI) between 30.0 to 40.0 kg/m2;

• Willingness and ability to comply with the study requirements;

• Ability to understand and sign informed consent;

• If woman of childbearing potential, she agrees to adopt effective contraceptive methods.

Exclusion Criteria:

• Pregnant or breastfeeding women;

• History of obesity with a known cause (e.g., hypothyroidism, Cushing's disease);

• Under treatment with perindopril or other angiotensin converting enzyme (ACE) inhibitor, or with an angiotensin receptor blocker (ARB) or a renin inhibitor;

• Hypertension diagnosed at screening;

• Significant variation in weight (more 10%) in the past 3 months before screening visit;

• History of anorexia nervosa, bulimia, or binge-eating disorder;

• Systolic blood pressure <110 mmHg;

• History of hypersensitivity to perindopril, or related compounds, or to any of the inactive ingredients;

• History of angioedema associated with previous ACE inhibitor therapy;

• History of idiopathic or hereditary angioedema;

• Treatment with concomitant medication affecting weight loss (e.g. metformin) starting within the 3 months prior to screening;

• Treatment with concomitant medication that might interfere with the absorption, distribution, metabolism or elimination of perindopril, or, is likely to compromise the safety of subject (e.g. diuretics in patients with salt and/or volume depletion, insulin or oral antidiabetics in patients prone to develop hypoglycemic episodes, lithium, vasodilators in patients prone to develop hypotension, tricyclic antidepressants, antipsychotics, anesthetics, gold, potassium supplements or potassium-containing salt substitutes);

• Treatment with any investigational drug or device within 1 month before the start of the run-in period;

• Moderate to severe hepatic impairment (Child-Pugh score ≥ 7) or moderate to severe renal impairment (glomerular filtration rate (GFR) ≤ 59 ml/min);

• Unstable coronary artery disease;

• Aortic and mitral valve stenosis / hypertrophic cardiomyopathy

• Hemodialysis patients;

• Kidney transplantation;

• Anaphylactoid reactions during low-density lipoproteins (LDL) apheresis;

• Neutropenia/agranulocytosis/thrombocytopenia/anemia;

• Patients undergoing major surgery or during anesthesia with agents that produce hypotension;

• Hyperkalemia;

• Any other condition or therapy that the study physician considers to make the subject unsuitable for this study