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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Dexa Medica Group
Sponsor:
Information provided by (Responsible Party):
Dexa Medica Group
ClinicalTrials.gov Identifier:
NCT01733459
First received: November 21, 2012
Last updated: March 7, 2014
Last verified: March 2014
  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 Intervention Phase
Polycystic Ovary Syndrome (PCOS)
Drug: DLBS3233
Drug: Metformin XR
Drug: Placebo caplet of Metformin XR
Drug: Placebo capsule of DLBS3233
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Role of DLBS3233 in the Management of Polycystic Ovary Syndrome (PCOS)

Resource links provided by NLM:


Further study details as provided by Dexa Medica Group:

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)


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).



Estimated Enrollment: 124
Study Start Date: March 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Inlacin
Drug: Placebo caplet of Metformin XR
1 placebo caplet of Metformin XR twice daily for 6 months
Other Name: 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 Name: Glumin XR
Drug: Placebo capsule of DLBS3233
1 placebo capsule of DLBS3233 once daily for 6 months
Other Name: Placebo capsule of Inlacin

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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01733459

Contacts
Contact: Andon Hestiantoro, dr., SpOG(K) +62815 1052 6366 hestiantoro@gmail.com
Contact: Wiryawan Permadi, Dr. dr., SpOG(K) +62811 2090 06 wiryawan_permadi@yahoo.com

Locations
Indonesia
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Padjadjaran, Hasan Sadikin Hospital Recruiting
Bandung, West Java, Indonesia, 40161
Contact: Wiryawan Permadi, Dr. dr., SpOG(K)    +62811 2090 06    wiryawan_permadi@yahoo.com   
Contact: Tono Djuwantono, Dr. dr., SpOG(K),, M.Kes    +62811 2250 60    djuwantono@yahoo.com   
Principal Investigator: Wiryawan Permadi, Dr. dr., SpOG(K)         
Sub-Investigator: Tono Djuwantono, Dr. dr., SpOG(K), M.Kes         
Sub-Investigator: Mulyanusa A. Ritonga, Dr., SpOG         
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Indonesia, dr. Cipto Mangunkusumo Hospital Recruiting
Jakarta, Indonesia, 10430
Contact: Andon Hestiantoro, dr., SpOG(K)    +62815 1052 6366    hestiantoro@gmail.com   
Contact: Kanadi Sumapraja, dr., SpOG(K), MSc    +62816 1821 604    kanadisuma@yahoo.com   
Principal Investigator: Andon Hestiantoro, dr., SpOG(K)         
Sub-Investigator: Budi Wiweko, dr., SpOG(K)         
Sub-Investigator: Kanadi Sumapraja, dr., SpOG(K), MSc         
Sub-Investigator: R. Muharam, dr., SpOG(K)         
Sub-Investigator: Cynthia Agnes Susanto, dr., B. Med. Sc         
Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: Dexa Medica Group
ClinicalTrials.gov Identifier: NCT01733459     History of Changes
Other Study ID Numbers: DLBS3233-0811
Study First Received: November 21, 2012
Last Updated: March 7, 2014
Health Authority: Indonesia: National Agency of Drug and Food Control

Keywords provided by Dexa Medica Group:
PCOS, DLBS3233, metformin,oral anti-hyperglycemic agent

Additional relevant MeSH terms:
Polycystic Ovary Syndrome
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Hypoglycemic Agents
Metformin
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014