Efficacy and Safety of DLBS3233 in Subjects With Polycystic Ovary Syndrome (PCOS) | RxWiki

Efficacy and Safety of DLBS3233 in Subjects With Polycystic Ovary Syndrome (PCOS)

Overview[ - collapse ][ - ]

Purpose	This is a 2-arm, randomized, double-blind, double-dummy, and controlled clinical study, with 6 months of treatment to evaluate the clinical and metabolic efficacy of DLBS3233 in improving reproductive parameters and to evaluate the safety of DLBS3233 in women with polycystic ovary syndrome compared with metformin, as an active control.
Condition	Polycystic Ovary Syndrome (PCOS)
Intervention	Drug: DLBS3233 Drug: Metformin XR Drug: Placebo caplet of Metformin XR Drug: Placebo capsule of DLBS3233
Phase	Phase 3
Sponsor	Dexa Medica Group
Responsible Party	Dexa Medica Group
ClinicalTrials.gov Identifier	NCT01733459
First Received	November 21, 2012
Last Updated	March 7, 2014
Last verified	March 2014

Tracking Information[ + expand ][ + ]

First Received Date	November 21, 2012
Last Updated Date	March 7, 2014
Start Date	March 2013
Estimated Primary Completion Date	February 2015
Current Primary Outcome Measures	HOMA-IR reduction [Time Frame: 6 months] [Designated as safety issue: No]HOMA-IR reduction from baseline to Month 6th (end of study)
Current Secondary Outcome Measures	Response rate: number of subjects having normalization of menses [Time Frame: 6 months] [Designated as safety issue: No]Response rate: number of subjects having normalization of menses within 6 months of treatment Response rate: pregnancy [Time Frame: 6 months] [Designated as safety issue: No]Response rate: pregnancy within 6 months of treatment Reduction of BMI [Time Frame: 1, 2, 3, 4, 5, and 6 Months] [Designated as safety issue: No]Reduction of BMI from baseline to every follow-up time-point evaluation Change of body fat composition [Time Frame: 1, 2, 3, 4, 5, and 6 months] [Designated as safety issue: No]Change of body fat composition from baseline to every follow-up time-point evaluation Change of waist circumference [Time Frame: 1, 2, 3, 4, 5, and 6 months] [Designated as safety issue: No]Change of waist circumference from baseline to every follow-up time-point evaluation Reduction of S/A ratio [Time Frame: 3 and 6 months] [Designated as safety issue: No]Reduction (indicating improvement) of S/A ratio (i.e. ratio of mean stromal echogenicity to mean echogenicity of entire ovary) from baseline to Month 3rd and Month 6th (end of study) Reduction of free testosterone level (calculated) [Time Frame: 6 months] [Designated as safety issue: No]Reduction of free testosterone level (calculated) from baseline to Month 6th (end of study) Change of luteinizing hormone (LH) level [Time Frame: 6 months] [Designated as safety issue: No]Change of luteinizing hormone (LH) level from baseline to Month 6th (end of study) Change of luteinizing hormone (LH) / follicle stimulating hormone (FSH) ratio [Time Frame: 6 months] [Designated as safety issue: No]Change of luteinizing hormone (LH) / follicle stimulating hormone (FSH) ratio from baseline to Month 6th (end of study) Change of Ferriman-Gallwey Score [Time Frame: 3 and 6 months] [Designated as safety issue: No]Change of Ferriman-Gallwey Score from baseline to Month 3rd and Month 6th (end of study) Improvement of glucose tolerance [Time Frame: 3 and 6 months] [Designated as safety issue: No]Improvement of glucose tolerance (reduction of FPG and 2-hour PPPG) from baseline to Month 3rd and Month 6th (end of study) Fasting insulin level reduction [Time Frame: 3 and 6 months] [Designated as safety issue: No]Fasting insulin level reduction from baseline to Month 3rd and Month 6th (end of study) HOMA-IR reduction [Time Frame: 3 months] [Designated as safety issue: No]HOMA-IR reduction from baseline to Month 3rd Lipid profile improvement [Time Frame: 3 and 6 months] [Designated as safety issue: No]Lipid profile improvement (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides level) from baseline to Month 3rd and Month 6th (end of study) Vital signs [Time Frame: 1, 2, 3, 4, 5, and 6 months] [Designated as safety issue: Yes]Vital signs (blood pressure, pulse rate, respiration rate) from baseline to every follow-up time-point evaluation Electrocardiography (ECG) [Time Frame: 6 months] [Designated as safety issue: Yes]Electrocardiography (ECG) from baseline to Month 6th (end of study) Liver function [Time Frame: 6 months] [Designated as safety issue: Yes]Liver function (serum AST, ALT, alkaline phosphatase, γ-glutamyl transferase) from baseline to Month 6th (end of study) Renal function [Time Frame: 6 months] [Designated as safety issue: Yes]Renal function (serum creatinine, BUN) from baseline to Month 6th (end of study) Number of adverse events and subjects with events [Time Frame: During 6 months] [Designated as safety issue: Yes]Adverse events as well as number of events and subjects experiencing the events will be observed and evaluated throughout study period (6 months) and until all adverse events have been recovered or stabilized Ovulation rate [Time Frame: 3.5 months and 5.5 months] [Designated as safety issue: No]Presence of ovulation will be observed using trans-vaginal USG at Month 3.5th and Month 5.5th. On Day 12th of the menstrual cycle, the USG will be performed on the subject. If there is no dominant follicle found on Day 12th, a serial USG examination will be performed at the interval of 3 days, up to Day 18th. On USG, when there is dominant follicle found, the presence of ovulation will be confirmed by measuring the progesterone level in the next 7 days. If until Day 18th there is no dominant follicle found, the ovulation is counted as absent. Change of Anti Mullerian Hormone (AMH) level [Time Frame: 6 Months] [Designated as safety issue: No]Change of Anti Mullerian Hormone (AMH) level from baseline to the end of study This additional secondary endpoint is site-specific (applicable only for site 01, i.e. Dr. Cipto Mangunkusumo Hospital, Jakarta).

Descriptive Information[ + expand ][ + ]

Brief Title	Efficacy and Safety of DLBS3233 in Subjects With Polycystic Ovary Syndrome (PCOS)
Official Title	The Role of DLBS3233 in the Management of Polycystic Ovary Syndrome (PCOS)
Brief Summary	This is a 2-arm, randomized, double-blind, double-dummy, and controlled clinical study, with 6 months of treatment to evaluate the clinical and metabolic efficacy of DLBS3233 in improving reproductive parameters and to evaluate the safety of DLBS3233 in women with polycystic ovary syndrome compared with metformin, as an active control.
Detailed Description	There will be 2 groups of treatment; each group will consist of 62 subjects with the treatment regimens : - Treatment I : 1 capsule of DLBS3233 100 mg (once daily) and 1 placebo caplet of Metformin XR (twice daily) - Treatment II : 1 caplet of Metformin XR 750 mg (twice daily) and 1 placebo capsule of DLBS3233 (once daily) for 6 months of treatment. Clinical examination to evaluate the efficacy of the investigational drug will be performed at baseline and every interval of 1 month. Laboratory examinations to evaluate the metabolic efficacy parameters and ultrasonography (USG) examination will be performed at baseline, Month 3rd, and end of study (Month 6th). In addition to that, USG will also be performed about 2 weeks after Month 3rd (Month 3.5th) and after Month 5th (Month 5.5th). Laboratory examinations to evaluate the reproductive efficacy parameters (reproductive hormone levels) and safety, at baseline and Month 6th (end of study). General counseling on lifestyle modification will be provided to the subjects by the assigned Nutritionist. All study subjects should follow a lifestyle modification. Evaluation on subjects' performance on lifestyle modification will be conducted every follow-up visit by Investigator, but particularly at baseline, Month 3rd, and end of study (Month 6th) by the Nutritionist.
Study Type	Interventional
Study Phase	Phase 3
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Condition	Polycystic Ovary Syndrome (PCOS)
Intervention	Drug: DLBS3233 1 DLBS3233 capsule 100 mg once daily for 6 months Other Names: InlacinDrug: Metformin XR 1 Metformin XR caplet 750 mg twice daily for 6 months Other Names: Glumin XRDrug: Placebo caplet of Metformin XR 1 placebo caplet of Metformin XR twice daily for 6 months Other Names: Placebo caplet of Glumin XRDrug: Placebo capsule of DLBS3233 1 placebo capsule of DLBS3233 once daily for 6 months Other Names: Placebo capsule of Inlacin
Study Arm (s)	Experimental: Treatment I 1 DLBS3233 capsule 100 mg (once daily) and 1 placebo caplet of Metformin XR (twice daily) Active Comparator: Treatment II 1 Metformin XR caplet 750 mg (twice daily) and 1 placebo capsule of DLBS3233 (once daily)

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	124
Estimated Completion Date	February 2015
Estimated Primary Completion Date	December 2014
Eligibility Criteria	Inclusion Criteria: - Female subjects in reproductive age (i.e. 18-40 years) - Subject with a diagnosis of polycystic ovary syndrome confirmed by two of the Rotterdam Criteria - Subject with insulin resistance defined by: HOMA-IR of > 2.00 Exclusion Criteria: - Pregnant and lactating women - Subjects known to have Cushing's syndrome, late onset of congenital adrenal hyperplasia, androgen-secreting tumors, uncontrolled thyroid disease, hyperprolactinemia - Known to have current medical condition, which, is judged by the Investigator could jeopardize subject's health or interfere with the study evaluation, such as diabetes mellitus, uncontrolled hypertension, other cardiovascular diseases, acute or chronic infections, and any known malignancies - Impaired renal function (serum creatinine level > 1.5 ULN) - Impaired liver function (serum ALT level ≥ 2.5 ULN) - Medically-assisted weight loss with medications or surgical procedures - Currently having laparoscopic ovarian diathermy (LOD) - Currently under treatment with in vitro fertilization (IVF) techniques - Have been regularly taking any medications which affect insulin sensitivity as well as reproductive function (i.e. ovulation, menstrual cycle), within ≤ 3 months prior to screening - Participating in other clinical trial within 30 days prior to screening
Gender	Female
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Andon Hestiantoro, dr., SpOG(K) +62815 1052 6366 hestiantoro@gmail.com
Location Countries	Indonesia

Administrative Information[ + expand ][ + ]

NCT Number	NCT01733459
Other Study ID Numbers	DLBS3233-0811
Has Data Monitoring Committee	No
Information Provided By	Dexa Medica Group
Study Sponsor	Dexa Medica Group
Collaborators	Not Provided
Investigators	Principal Investigator: Andon Hestiantoro, dr., SpOG(K) Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Indonesia, dr. Cipto Mangunkusumo Hospital, Jakarta, IndonesiaPrincipal Investigator: Wiryawan Permadi, Dr. dr., SpOG(K) Department of Obstetrics and Gynecology, Faculty of Medicine, University of Padjadjaran, Hasan Sadikin Hospital, Bandung, Indonesia
Verification Date	March 2014

Locations[ + expand ][ + ]

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Padjadjaran, Hasan Sadikin Hospital	Bandung, West Java, Indonesia, 40161 Contact: Wiryawan Permadi, Dr. dr., SpOG(K) \| +62811 2090 06 \| wiryawan_permadi@yahoo.com Principal Investigator: Wiryawan Permadi, Dr. dr., SpOG(K) Recruiting
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Indonesia, dr. Cipto Mangunkusumo Hospital	Jakarta, Indonesia, 10430 Contact: Andon Hestiantoro, dr., SpOG(K) \| +62815 1052 6366 \| hestiantoro@gmail.com Principal Investigator: Andon Hestiantoro, dr., SpOG(K) Recruiting