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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Polycystic Ovary Syndrome (PCOS)

Intervention / Treatment
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* Drug: DLBS3233
* Drug: Metformin XR
* Drug: Placebo caplet of Metformin XR
* Drug: Placebo capsule of DLBS3233


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment I<br>1 DLBS3233 capsule 100 mg (once daily) and 1 placebo caplet of Metformin XR (twice daily) | Drug: DLBS3233<br>* 1 DLBS3233 capsule 100 mg once daily for 6 months<br>* Other names: Inlacin;Drug: Placebo caplet of Metformin XR<br>* 1 placebo caplet of Metformin XR twice daily for 6 months<br>* Other names: Placebo caplet of Glumin XR;|
| Active Comparator: Treatment II<br>1 Metformin XR caplet 750 mg (twice daily) and 1 placebo capsule of DLBS3233 (once daily) | Drug: Metformin XR<br>* 1 Metformin XR caplet 750 mg twice daily for 6 months<br>* Other names: Glumin XR;Drug: Placebo capsule of DLBS3233<br>* 1 placebo capsule of DLBS3233 once daily for 6 months<br>* Other names: Placebo capsule of Inlacin;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PCOS, DLBS3233, metformin,oral anti-hyperglycemic agent