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

The Role of DLBS3233 in the Management of Polycystic Ovary Syndrome (PCOS)

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.

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome (PCOS)
• Intervention / Treatment: Drug: DLBS3233; Drug: Placebo caplet of Metformin XR; Drug: Metformin XR; Drug: Placebo capsule of DLBS3233

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
• Enrollment (Actual): 124
• Phase: Phase 3

Contacts and Locations

Study Locations

• Indonesia
  • Jakarta, Indonesia, 10430
    • Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Indonesia, dr. Cipto Mangunkusumo Hospital
  • West Java
    • Bandung, West Java, Indonesia, 40161
      • Department of Obstetrics and Gynecology, Faculty of Medicine, University of Padjadjaran, Hasan Sadikin Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment I; 1 DLBS3233 capsule 100 mg (once daily) and 1 placebo caplet of Metformin XR (twice daily)	Drug: DLBS3233; 1 DLBS3233 capsule 100 mg once daily for 6 months; Other Names: Inlacin; Drug: Placebo caplet of Metformin XR; 1 placebo caplet of Metformin XR twice daily for 6 months; Other Names: Placebo caplet of Glumin XR
ACTIVE_COMPARATOR: Treatment II; 1 Metformin XR caplet 750 mg (twice daily) and 1 placebo capsule of DLBS3233 (once daily)	Drug: Metformin XR; 1 Metformin XR caplet 750 mg twice daily for 6 months; Other Names: Glumin XR; Drug: Placebo capsule of DLBS3233; 1 placebo capsule of DLBS3233 once daily for 6 months; Other Names: Placebo capsule of Inlacin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HOMA-IR reduction	HOMA-IR reduction from baseline to Month 6th (end of study)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of S/A ratio	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)	3 and 6 months
Reduction of free testosterone level (calculated)	Reduction of free testosterone level (calculated) from baseline to Month 6th (end of study)	6 months
Change of luteinizing hormone (LH) level	Change of luteinizing hormone (LH) level from baseline to Month 6th (end of study)	6 months
Change of luteinizing hormone (LH) / follicle stimulating hormone (FSH) ratio	Change of luteinizing hormone (LH) / follicle stimulating hormone (FSH) ratio from baseline to Month 6th (end of study)	6 months
Change of Ferriman-Gallwey Score	Change of Ferriman-Gallwey Score from baseline to Month 3rd and Month 6th (end of study)	3 and 6 months
Improvement of glucose tolerance	Improvement of glucose tolerance (reduction of FPG and 2-hour PPPG) from baseline to Month 3rd and Month 6th (end of study)	3 and 6 months
Fasting insulin level reduction	Fasting insulin level reduction from baseline to Month 3rd and Month 6th (end of study)	3 and 6 months
HOMA-IR reduction	HOMA-IR reduction from baseline to Month 3rd	3 months
Lipid profile improvement	Lipid profile improvement (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides level) from baseline to Month 3rd and Month 6th (end of study)	3 and 6 months
Liver function	Liver function (serum AST, ALT, alkaline phosphatase, γ-glutamyl transferase) from baseline to Month 6th (end of study)	6 months
Renal function	Renal function (serum creatinine, BUN) from baseline to Month 6th (end of study)	6 months
Number of adverse events and subjects with events	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	During 6 months

Collaborators and Investigators

• Sponsor: Dexa Medica Group
• 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, Indonesia; Principal Investigator: Wiryawan Permadi, Dr., dr., SpOG(K), Department of Obstetrics and Gynecology, Faculty of Medicine, University of Padjadjaran, Hasan Sadikin Hospital, Bandung, Indonesia

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (ACTUAL): April 1, 2018
• Study Completion (ACTUAL): June 1, 2018

Study Registration Dates

• First Submitted: November 21, 2012
• First Submitted That Met QC Criteria: November 21, 2012
• First Posted (ESTIMATE): November 27, 2012

Study Record Updates

• Last Update Posted (ACTUAL): July 26, 2018
• Last Update Submitted That Met QC Criteria: July 24, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: PCOS, DLBS3233, metformin,oral anti-hyperglycemic agent
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome; Syndrome; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: DLBS3233-0811