PCOS Treatment Using DLBS3233, Metformin, and Combination of Both (POSITIF)

Dexa Medica

Status and phase: Completed; Phase 3

Conditions: Insulin Resistance; Polycystic Ovary Syndrome (PCOS)

Treatments: Drug: DLBS3233; Drug: Metformin XR; Drug: Placebo metformin; Drug: Placebo DLBS3233

Study type: Interventional

Funder types: Industry

Identifiers

NCT01999686

DLBS3233-1013

Details and patient eligibility

About

This is a 3-arm, randomized, double-blind, double-dummy, and controlled clinical study over 6 months of treatment to evaluate the metabolic and clinical efficacy as well as the safety of DLBS3233 alone, metformin and combination of both, in improving metabolic and reproductive parameters.

Full description

There will be 3 groups of treatment (N = 186), each consist of 62 subjects, as the following:

• Treatment I : DLBS3233 100 mg once daily
• Treatment II : Metformin XR 750 mg twice daily
• Treatment III : DLBS3233 100 mg once daily and Metformin XR 750 mg twice daily.

Laboratory examination to evaluate metabolic efficacy parameters will be performed at baseline, Month 3rd, and end of study (Month 6th).

Clinical and laboratory examination to evaluate the reproductive efficacy parameters using trans-vaginal USG and biomarkers (such as reproductive hormones) will be performed at baseline to the end of study.

Safety examination will be performed at baseline and end of study. Occurrence of adverse event will be observed along the study conduct.

Enrollment: 186 patients

Sex: Female

Ages: 18 to 40 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Signed written informed consent prior to participation in the study.

2. Female subjects in reproductive age (i.e. 18-40 years) willing to conceive.

3. Subject with a diagnosis of polycystic ovary syndrome confirmed by two of the following (Rotterdam Criteria):

   • Hyperandrogenism (defined by elevated free testosterone concentration; or Ferriman-Gallwey Score of ≥ 8).
   • Ovarian dysfunction indicated by menstrual irregularity: oligomenorrhea (cycles of > 35 days), or amenorrhea (no menses in the last of 3 months) after negative screening pregnancy test.
   • Polycystic ovary as shown by ultrasonography (USG).

4. Subject with insulin resistance defined by : HOMA-IR of > 2.00.

5. Subject with body mass index (BMI) of 19-35 inclusive.

6. Able to take oral medication.

Exclusion criteria

1. Pregnant or lactating women (urinary pregnancy test will be applied at screening).

2. Based on previous or current medical (either laboratory or clinical) examination, subjects known to have any of the following conditions:

   • Cushing's syndrome, late onset of congenital adrenal hyperplasia, androgen-secreting tumors, uncontrolled thyroid disease, hyperprolactinemia.

3. Known to have the following medical condition:

   • Diabetes mellitus,
   • Uncontrolled hypertension
   • Symptomatic cardiovascular diseases:
   • Acute or chronic infections at baseline.
   • Any known malignancies.

4. History of gynecological surgery.

5. Impaired renal function

6. Impaired liver function

7. Medically-assisted weight loss with medications or surgical procedures.

8. Currently having laparoscopic ovarian diathermy (LOD).

9. Currently under treatment with in vitro fertilization (IVF) techniques.

10. Have been regularly taking any of the following medications, within ≤ 3 months prior to screening, such as:

    • Clomiphene citrate
    • Insulin sensitizers, i.e. metformin and thiazolidinediones
    • Aromatase inhibitors, such as: anastrozole, letrozole
    • Glucocorticoids
    • Gonadotropins
    • Gonadotropin-releasing hormone agonists (GnRHa)
    • Oral contraceptive pills (OCPs)
    • Antiandrogens, such as: spironolactone, cyproterone acetate (CPA), and flutamide
    • Any traditional or herbal medicines

11. Participating in other clinical trial within 30 days prior to screening.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

186 participants in 3 patient groups

Treatment I : DLBS3233

Experimental group

Description:

DLBS3233 100 mg capsule once daily, and Placebo metformin caplet twice daily; orally, for 6 months

Treatment:

Drug: Placebo metformin

Drug: DLBS3233

Treatment II : Metformin

Active Comparator group

Description:

Metformin XR 750 mg caplet twice daily, and Placebo DLBS3233 once daily; orally, for 6 months

Treatment:

Drug: Placebo DLBS3233

Drug: Metformin XR

Treatment III : Combination DLBS3233 and Metformin

Experimental group

Description:

DLBS3233 100 mg capsule once daily, and Metformin XR 750 mg caplet twice daily; orally, for 6 months.

Treatment:

Drug: Metformin XR

Drug: DLBS3233