Influence of Carboxypeptidase D (CPD) Gene on Body Weight and Fat Mass Reduction by Perindopril in Obese Subjects (GPD-01-01)
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|ClinicalTrials.gov Identifier: NCT02777489|
Recruitment Status : Terminated (Unproven hypothesis)
First Posted : May 19, 2016
Last Update Posted : August 3, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Obesity||Drug: Perindopril||Phase 2|
The study consists of 2 periods and 4 visits (V): a run-in period of at least 4 weeks (V1 to V2) and a 12-week perindopril treatment period (V2 to V4).
After written informed consent, patients will undergo screening evaluations (V1). Patients who meet the selection criteria will enter a run-in period of 4 weeks where they will be given dietary and exercise counseling as standardized non-drug therapy. After the run-in period (V2), patients will start the pharmacological therapy period where they will receive perindopril 8 mg, once daily, for 12 weeks, concomitantly with the previously established standardized non-drug therapy.
During the 12-week pharmacological treatment, patients will attend an intermediate study visit (V3) at approximately 6 weeks and a final visit (V4) for efficacy and safety assessments.
Body weight, body mass index (BMI), waist and hip circumference, and body fat mass estimation will be assessed at every study visit.
A total of 160 subjects will be enrolled, to have approximately 120 subjects evaluable.
After V2, patients will be administered perindopril 8 mg, once daily, for 12 weeks, concomitantly with the previously established standardized non-pharmacological therapy.
Blood sampling for clinical safety laboratory assessments (hematology and plasma biochemistry) will be collected at the screening, at the end of the run-in period, at the intermediate treatment visit, and at the end of the perindopril treatment period.
At the screening, blood will also be collected for CPD genotyping, but the results will remain blinded until database closure.
Safety will be evaluated through the assessment of treatment-emergent adverse events, vital signs and clinical laboratory tests. Adverse events will be monitored throughout the study. Vital signs will be recorded at each scheduled visit. Clinical safety laboratory parameters will be collected at screening, end of the run-in period, at the intermediate treatment visit, and at the end of the treatment period.
Abnormalities in vital signs and laboratory parameters will be assessed by the clinical investigator in terms of clinical relevance. Clinically significant abnormalities in clinical laboratory and vital signs will be reported as adverse events.
Associations between CPD SNPs genotypes and patient response will be assessed through the appropriate statistical methods. The primary efficacy analysis will compare the response rate in the group of subjects with the SNPs of interest and the group of the remaining subjects. A logistic regression model will be used to assess the group differences. Weight and fat mass at the start of the perindopril treatment period and gender will be used as covariates. Other covariates will be investigated for exploratory purposes, but will not be included in the model where main treatment effects are tested and compared. All the secondary efficacy endpoints will be assessed using analysis of covariance (ANCOVA). In general, the principles applied for the primary efficacy analysis will be replicated for the secondary efficacy analysis.
Adverse events will be tabulated and summarized according to system organ class (SOC) and preferred term (PT).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||140 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Influence of Single Nucleotide Polymorphisms of Carboxypeptidase D (CPD) Gene on Body Weight and Fat Mass Reduction by Perindopril in Obese Subjects: A Phase II, Multicenter, Double-blind Study|
|Study Start Date :||February 18, 2016|
|Actual Primary Completion Date :||January 18, 2017|
|Actual Study Completion Date :||April 27, 2017|
Experimental: Perindopril Bluepharma 8 mg
Each participant will have an at least 4-week run-in period, followed by a 6 weeks treatment period with Perindopril 8 mg.
Perindopril Bluepharma 8 mg tablets, daily, during approximately 12 weeks
- Response rate, defined as the proportion of patients who will lose at least 3% of body weight and/or at least 3% of fat mass from end of the run-in period to the end of the perindopril treatment period. [ Time Frame: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks ]
- End vs start of treatment relative change in body weight. [ Time Frame: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks ]
- End vs start of treatment relative change in fat mass. [ Time Frame: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks ]
- End vs start of treatment relative change in waist circumference. [ Time Frame: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks ]
- End vs start of treatment relative change in hip circumference. [ Time Frame: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks ]
- End vs start of treatment relative change in fasting lipid profile. [ Time Frame: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks ]
- Frequency and type of adverse events. [ Time Frame: From V1 until the end of the perindopril treatment period, , up to 16 weeks ]
- Response rate, defined as the proportion of patients who will lose at least 5% of body weight and/or at least 5% of fat mass from end of the run-in period to the end of the perindopril treatment period. [ Time Frame: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02777489
|Unidade de Saúde Familiar Escariz|
|Arouca, Portugal, 4540-297|
|Centro Hospitalar do Baixo Vouga (CHBV), EPE|
|Aveiro, Portugal, 3814-501|
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|Porto, Portugal, 4200-319|
|Unidade de Saúde Familiar Arca d'Água|
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|Unidade de Cuidados de Saúde Personalizados Carvalhido|
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|Unidade Local de Saúde do Alto Minho (ULSAM), E.P.E.|
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|Unidade de Saúde Familiar Santo André de Canidelo|
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|Centro Hospitalar V.N.Gaia/Espinho (CHVNG/E)- Endocrinology|
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|Centro Hospitalar Vila Nova de Gaia/Espinho (CHVNG/E)|
|Vila Nova de Gaia, Portugal, 4434-502|