PCOS Treatment Using DLBS3233, Metformin, and Combination of Both | RxWiki

PCOS Treatment Using DLBS3233, Metformin, and Combination of Both

Overview[ - collapse ][ - ]

Purpose	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.
Condition	Polycystic Ovary Syndrome (PCOS) Insulin Resistance
Intervention	Drug: DLBS3233 Drug: Metformin XR Drug: Placebo metformin Drug: Placebo DLBS3233
Phase	Phase 3
Sponsor	Dexa Medica Group
Responsible Party	Dexa Medica Group
ClinicalTrials.gov Identifier	NCT01999686
First Received	November 26, 2013
Last Updated	March 7, 2014
Last verified	March 2014

Tracking Information[ + expand ][ + ]

First Received Date	November 26, 2013
Last Updated Date	March 7, 2014
Start Date	April 2014
Estimated Primary Completion Date	December 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	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) 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) 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 waist circumference [Time Frame: 1, 2, 3, 4, 5, and 6 months] [Designated as safety issue: No]1, 2, 3, 4, 5, and 6 months Response rate: presence of ovulation [Time Frame: menstrual cycle of Month 3rd up to that of Month 6th] [Designated as safety issue: No]Presence of ovulation will be evaluated using trans-vaginal USG to find dominant follicle(s), at the day/period of ovulation, starting from menstrual cycle of Month 3rd up to Month 6th. Measurement of progesterone level will be performed 7 days after the finding of dominant follicle on USG examination to confirm the presence of ovulation. Change of endometrium thickness [Time Frame: 3 to 6 months] [Designated as safety issue: No]Change of endometrium thickness will be measured by using trans-vaginal USG at basal condition and at the day/period of ovulation Improvement of S/A ratio [Time Frame: 3 to 6 months] [Designated as safety issue: No]Improvement from baseline of the S/A ratio (defined as the ratio between stromal and total area of median ovarian section) will be measured using trans-vaginal USG (trans-longitudinal measurement) at Baseline, menstrual cycle of Month 3rd, and menstrual cycle of Month 6th at basal condition. Response rate: normalization of menses (ovulatory cycle) [Time Frame: 6 months] [Designated as safety issue: No]Normalization of menses (ovulatory cycle) within 6 months of treatment. Note: This secondary endpoint will be applied only for subjects with menstrual irregularity at baseline. Response rate: pregnancy [Time Frame: 6 months] [Designated as safety issue: No]Pregnancy within 6 months of treatment. Improvement in Ferriman-Gallwey Score [Time Frame: 3 and 6 months] [Designated as safety issue: No]Improvement in Ferriman-Gallwey Score from baseline to Month 3rd and Month 6th (the end of study) Reduction of free testosterone level [Time Frame: 6 months] [Designated as safety issue: No]Reduction of free testosterone level 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) 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) will be measured at baseline and every interval of 1 month over the 6 months of treatment. Electrocardiography (ECG) [Time Frame: 6 months] [Designated as safety issue: Yes]Electrocardiography (ECG) will be performed at baseline and Month 6th (end of study) Liver function [Time Frame: 6 months] [Designated as safety issue: Yes]Liver function (levels of serum AST, ALT, alkaline phosphatase) will be measured at baseline and Month 6th (end of study) Renal function [Time Frame: 6 months] [Designated as safety issue: Yes]Renal function (levels of serum creatinine, BUN) will be measured at baseline and 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

Descriptive Information[ + expand ][ + ]

Brief Title	PCOS Treatment Using DLBS3233, Metformin, and Combination of Both
Official Title	Polycystic Ovary Syndrome Treatment Using DLBS3233, Metformin, and Combination of Both, and Its Relation to Fertility
Brief Summary	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.
Detailed 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.
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) Insulin Resistance
Intervention	Drug: DLBS3233 Other Names: InlacinDrug: Metformin XR Other Names: Glumin XRDrug: Placebo metformin Placebo metformin has the same ingredients with Metformin XR caplet, except that it does not contain the active substance (metformin). Other Names: Placebo metforminDrug: Placebo DLBS3233 Placebo DLBS3233 has the same ingredients with DLBS3233 capsule, except that it does not contain the active substance (DLBS3233). Other Names: Placebo DLBS3233
Study Arm (s)	Experimental: Treatment I : DLBS3233 DLBS3233 100 mg capsule once daily, and Placebo metformin caplet twice daily; orally, for 6 months Active Comparator: Treatment II : Metformin Metformin XR 750 mg caplet twice daily, and Placebo DLBS3233 once daily; orally, for 6 months Experimental: Treatment III : Combination DLBS3233 and Metformin DLBS3233 100 mg capsule once daily, and Metformin XR 750 mg caplet twice daily; orally, for 6 months.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Not yet recruiting
Estimated Enrollment	186
Estimated Completion Date	December 2015
Estimated Primary Completion Date	October 2015
Eligibility Criteria	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. 7. Able to participate, communicate well with the Investigators and willing to comply with the study protocol. 8. Able and willing to record any adverse events in the given patient's diary. 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, defined by the presence of its clinical symptoms (i.e. weight gain, central obesity, moon face, purplish skin striae, buffalo hump, severe fatigue and muscle weakness, high blood pressure, depression, cognitive impairment, hirsutism, acne, menstrual disorder). - Late onset of congenital adrenal hyperplasia, defined by the presence of its clinical symptoms (i.e. obesity, short stature, menstrual irregularities, androgenic alopecia, hirsutism, acne, precocious puberty, infertility). - Androgen-secreting tumors, defined by elevated free testosterone concentration and /or the presence of its clinical condition through USG examination. - Uncontrolled thyroid disease, defined by abnormal level of thyroid stimulating hormone (TSH) - Hyperprolactinemia, defined by elevated prolactin concentration. 3. Known to have the following medical condition: - Diabetes mellitus, defined as fasting plasma glucose (FPG) level of ≥ 126 mg/dL or a 2-hour plasma glucose (2h-PG) ≥ 200 mg/dL during a 75 gram oral glucose challenge test. - Uncontrolled hypertension defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg. - Other cardiovascular diseases: - Symptomatic ischaemic heart disease - Unstable angina pectoris - Heart failure - Acute or chronic infections at baseline. - Any known malignancies. 4. History of gynecological surgery. 5. Impaired renal function, as measured by the elevation of serum creatinine level ≥ 1.5 upper limit of normal. 6. Impaired liver function, as measured by the elevation of serum ALT level > 2.5 upper limit of normal. 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.
Gender	Female
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Soehartono Ds, Prof. Dr., SpOG-K +62811347720 batabsby@yahoo.com
Location Countries	Indonesia

Administrative Information[ + expand ][ + ]

NCT Number	NCT01999686
Other Study ID Numbers	DLBS3233-1013
Has Data Monitoring Committee	No
Information Provided By	Dexa Medica Group
Study Sponsor	Dexa Medica Group
Collaborators	Not Provided
Investigators	Principal Investigator: Soehartono Ds, Prof. dr., SpOG-K Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Airlangga, Dr. Soetomo Hospital, Surabaya, Indonesia.Principal Investigator: Arsana Wiyasa IW, Dr. dr., SpOG-K Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Brawijaya, Dr. Saiful Anwar Hospital, Malang, Indonesia.Principal Investigator: Putu Doster Mahayasa, dr., SpOG-K Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Udayana, Sanglah Hospital, Denpasar, Indonesia.Principal Investigator: Syarief Taufik, dr., SpOG-K Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, Diponegoro University, Dr. Kariadi Hospital, Semarang, Indonesia.Principal Investigator: Nusratuddin Abdullah, Dr. dr., SpOG-K, MARS Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Hasanuddin, Dr. Wahidin Sudirohusodo Hospital, Makasar, Indonesia.Principal Investigator: Iwan Darma Putra, dr., SpOG-K Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Lambung Mangkurat, Ulin Banjarmasin Hospital, Banjarmasin, Indonesia.Principal Investigator: Eddy Suparman, Prof. Dr. dr., SpOG-K Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Sam Ratulangi, Prof. Dr. Kandou Hospital, Manado, Indonesia.
Verification Date	March 2014

Locations[ + expand ][ + ]

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Lambung Mangkurat, Ulin Banjarmasin Hospital	Banjarmasin, Indonesia Contact: Iwan Darma Putra, dr., SpOG-K \| +62811503472 \| i_darmaputra@yahoo.com Principal Investigator: Iwan Darma Putra, dr., SpOG-K Not yet recruiting
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Udayana, Sanglah Hospital	Denpasar, Indonesia Contact: Putu Doster Mahayasa, dr., SpOG-K \| +628123812259 \| dmahayasa@gmail.com Principal Investigator: Putu Doster Mahayasa, dr., SpOG-K Not yet recruiting
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Hasanuddin, Dr. Wahidin Sudirohusodo Hospital	Makasar, Indonesia Contact: Nusratuddin Abdullah, Dr. dr., SpOG-K, MARS \| +6281342752561 \| nusraya@yahoo.com Principal Investigator: Nusratuddin Abdullah, Dr. dr., SpOG-K, MARS Not yet recruiting
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Brawijaya, Dr. Saiful Anwar Hospital	Malang, Indonesia Contact: Arsana Wiyasa IW, Dr. dr., SpOG-K \| +62811343876 \| abiyasa9@yahoo.com Principal Investigator: Arsana Wiyasa IW, Dr. dr., SpOG-K Not yet recruiting
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Sam Ratulangi, Prof. Dr. Kandou Hospital	Manado, Indonesia Contact: Eddy Suparman, Prof. Dr. dr., SpOG-K \| +62811431600 \| obsgyn_manado@yahoo.com.sg Principal Investigator: Eddy Suparman, Prof. Dr. dr., SpOG-K Not yet recruiting
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, Diponegoro University, Dr. Kariadi Hospital	Semarang, Indonesia Contact: Syarief Taufik, dr., SpOG-K \| +628112715580 \| tofik_obg@yahoo.com Principal Investigator: Syarief Taufik, dr., SpOG-K Not yet recruiting
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Airlangga, Dr. Soetomo Hospital.	Surabaya, Indonesia Contact: Soehartono Ds, Prof. dr., SpOG-K \| +62811347720 \| batabsby@yahoo.com Principal Investigator: Soehartono Ds, Prof. dr., SpOG-K Not yet recruiting