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CTRI Number  CTRI/2023/03/050791 [Registered on: 17/03/2023] Trial Registered Prospectively
Last Modified On: 01/11/2023
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   A study to examine the effect of Dydrogesterone Sustained Release Tablets 30 mg for the treatment of endometriosis associated pain in women. 
Scientific Title of Study   “A Phase III, Randomized, Double Blind, Single Dummy, Active Controlled, Prospective, Parallel Group, Comparative, Multicentric Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Dydrogesterone Sustained Release Tablets 30 mg versus Dydrogesterone Tablets 10 mg for the Treatment of Endometriosis in Women.” 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
CT/2022/44, Version No.: 00 and Dated Dec 01, 2022  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Rajasekhara Reddy Tamma 
Designation  Managing Director 
Affiliation  Clinwave Research Pvt. Ltd. 
Address  Clinwave Research Pvt. Ltd., # H. No.: 4-32-41/13, Plot No.: 38, Kamala Prasanna Nagar, Near Ramalayam Temple, Kukatpally, Hyderabad.

Hyderabad
TELANGANA
500072
India 
Phone  7989233379  
Fax    
Email  dr.sekhar@clinwave.co.in  
 
Details of Contact Person
Scientific Query
 
Name  Dr Rajasekhara Reddy Tamma 
Designation  Managing Director 
Affiliation  Clinwave Research Pvt. Ltd. 
Address  Clinwave Research Pvt. Ltd., # H. No.: 4-32-41/13, Plot No.: 38, Kamala Prasanna Nagar, Near Ramalayam Temple, Kukatpally, Hyderabad.

Hyderabad
TELANGANA
500072
India 
Phone  7989233379  
Fax    
Email  dr.sekhar@clinwave.co.in  
 
Details of Contact Person
Public Query
 
Name  Dr Rajasekhara Reddy Tamma 
Designation  Managing Director 
Affiliation  Clinwave Research Pvt. Ltd. 
Address  Clinwave Research Pvt. Ltd., # H. No.: 4-32-41/13, Plot No.: 38, Kamala Prasanna Nagar, Near Ramalayam Temple, Kukatpally, Hyderabad.

Hyderabad
TELANGANA
500072
India 
Phone  7989233379  
Fax    
Email  dr.sekhar@clinwave.co.in  
 
Source of Monetary or Material Support  
Ravenbhel Healthcare Pvt. Ltd., 16-17, EPIP, SIDCO, Kartholi, Bari-Brahamana, Samba-181133, Jammu and Kashmir, India. 
 
Primary Sponsor  
Name  Ravenbhel Healthcare Pvt. Ltd. 
Address  16-17, EPIP, SIDCO, Kartholi, Bari-Brahamana, Samba-181133, Jammu and Kashmir, India. 
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 9  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Nidhi Patel  Aatman Hospital  Clinical Research Room, 5, Anveshan Row House, Bopal Gam BRTS, Bopal-Ghuma Road, Bopal, Ahmedabad-380058.
Ahmadabad
GUJARAT 
9033019291

cr.aatman@gmail.com 
Dr Pallavi Singh  Chandani Hospital Pvt. Ltd.  Research Room, 9/60, Arya Nagar Road, Khalasi Line, Arya Nagar, Kanpur-208002.
Kanpur Nagar
UTTAR PRADESH 
9415133332

pi.chandanihospital@gmail.com 
Dr Rani Kumari L  Gandhi Medical College and Hospital  In Patient Block, 2nd Floor, Department of Gynecology, Musheerabad, Secunderabad-500003.
Hyderabad
TELANGANA 
9491657107

drranikumari.research@gmail.com 
Dr Seema Upadhyay  GSVM Medical College  Department of Obstetrics and Gynaecology, LLR Hospital, Swaroop Nagar, Kanpur-208002.
Kanpur Nagar
UTTAR PRADESH 
9455635389

seema993573@gmail.com 
Dr Archana Sinha  Indira Gandhi Institute of Medical Sciences (IGIMS)  Department of Obstetrics & Gynaecology, Sheikhpura, Patna-800014.
Patna
BIHAR 
9661599099

drarchanasinha35@gmail.com 
Dr Suchitra Narayan  Jawahar Lal Nehru (J.L.N) Medical College  Department of Obstetrics and Gynaecology, Kala Bagh, Ajmer-305001.
Ajmer
RAJASTHAN 
7627026609

narayan_jaiprakash@yahoo.com 
Dr Madhavender Jain  Maharaja Agrasen Superspeciality Hospital  Research Room, Central Spine, Agrasen Aspatal Marg, Sector 7, Vidyadhar Nagar,Jaipur-302039.
Jaipur
RAJASTHAN 
9413062961

madhvanderjain@gmail.com 
Dr Raja Bhattacharya  Medical College and Hospital, Kolkata  Department of Medicine, MCH Building, 4th Floor, 88 College Street, Kolkata-700073.
Kolkata
WEST BENGAL 
9477305539

rbrbhattacharya@gmail.com 
Dr Rahul Chandrakant Kumbhar  Prakash Institute of Medical Sciences & Research (PIMS&R)  Research Room, Urun-Islampur, Islampur-Sangali Road, Islampur, Tal-Walwa, Dist-Sangali-415409.
Sangli
MAHARASHTRA 
7775014777

prakashmc.research@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 9  
Name of Committee  Approval Status 
Ethics Committee, GSVM Medical College  Approved 
Institutional Ethics Committee for Human Research, Medical College and Hospital  Approved 
Institutional Ethics Committee, Aatman Hospital  Approved 
Institutional Ethics Committee, Chandani Hospital Pvt. Ltd.  Approved 
Institutional Ethics Committee, Gandhi Medical College/Gandhi Hospital  Approved 
Institutional Ethics Committee, Indira Gandhi Institute of Medical Sciences (IGIMS)  Approved 
Institutional Ethics Committee, Jawahar Lal Nehru Medical College  Approved 
Institutional Ethics Committee, Maharaja Agrasen Superspeciality Hospital  Approved 
Prakash Medical College Institutional Ethics Committee, Prakash Institute of Medical Sciences & Research  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: N809||Endometriosis, unspecified,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Dydrogesterone Sustained Release Tablets 30 mg & Placebo Tablets  Patients will be advised to take one tablet thrice a day orally, swallowed with water in the morning, afternoon and evening around same time every day for 90 days. Morning - One tablet of test product, Afternoon - One tablet of placebo matching test product & Evening - One tablet of placebo matching test product Treatment Period: 90 Days  
Comparator Agent  Dydrogesterone Tablets 10 mg  Patients will be advised to take one tablet thrice a day orally, swallowed with water in the morning, afternoon and evening around same time every day for 90 days. Morning - One tablet of reference product, Afternoon - One tablet of reference product & Evening - One tablet of reference product Treatment Period: 90 Days  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  45.00 Year(s)
Gender  Female 
Details  1. Female patients of aged between 18-45 years (both inclusive).
2. Patients diagnosed with endometriosis based on imaging studies i.e., USG.
3. Patients with endometriosis associated pelvic pain having a score of at least 30 mm on a 100 mm visual analog scale.
4. Patients having agreed to the use of double barrier contraception (use of the male condom along with either diaphragm, cervical cap, or copper T IUD).
5. Patients with ability to understand and provide written informed consent form, which must have been obtained prior to screening.
6. Patients willing to comply with all the protocol requirements. 
 
ExclusionCriteria 
Details  1. Patients with intolerance, contraindication or potential allergy/hypersensitivity to Dydrogesterone.
2. Patients with laparoscopic surgery for endometriosis within 6 months before screening.
3. Female patients who are pregnant or lactating or planning to become pregnant during the study period.
4. Females who are not ready to use acceptable contraceptive methods during study.
5. Patients with previous use of hormonal agents (e.g., GnRH agonists ≤ 6 months, Danazol ≤ 3 months or oral contraceptives ≤ 1 month before screening).
6. Patients who have achieved menopause or have premature ovarian insufficiency.
7. Patients undergoing treatment for infertility by assisted reproductive technologies or any other procedure.
8. Patients with known case of clinically significant cerebrovascular disease, cardiovascular disease, thyroid dysfunction, chronic uncontrolled systemic diseases like asthma, hypertension, collagen disorders, severe infections, that may affect patient safety.
9. Patients with any other significant concomitant gynecological disorder (fibroid etc.).
10. Patients with active or recent (within 6 months) arterial thromboembolic disease (e.g., angina, myocardial infarction) or venous thromboembolism (deep vein thrombosis, pulmonary embolism) or at high risk of venous or arterial thrombosis.
11. Patients regularly using analgesics not intended to relieve endometriosis associated chronic pelvic pain (e.g., using analgesics for osteoarthritis etc.).
12. Patients with hepatic dysfunction (SGOT & SGPT ≥ 3 X Upper Normal Limit) or renal dysfunction (serum creatinine ≥ 2.5 mg/dL).
13. Patients with any abnormality detected on ECG at the time of screening.
14. Patients with history of drug or alcohol abuse.
15. Patients with medical history of oncological conditions.
16. Patients with known case of HIV, Hepatitis B & C.
17. Patients with concurrent participation in another clinical trial within 30 days prior to signing informed consent.
18. Patients currently taking prohibited medications(s) listed and inability/unwillingness to discontinue them for the entire study period.
19. Patients with suspected inability or unwillingness to comply with the study procedures.
20. Patient with any condition which, in the judgment of the Investigator, may render the patient unable to complete the study or which may pose a significant risk to the patient. 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Pre-numbered or coded identical Containers 
Blinding/Masking   Participant and Investigator Blinded 
Primary Outcome  
Outcome  TimePoints 
Mean change in endometriosis associated pelvic pain from baseline to end of the study, assessed by a visual analogue scale (VAS; 0 mm means absence of pain, 100 mm means unbearable pain).  At Screening Visit (Visit 1),
Visit 2 (Day 1 / Baseline),
Visit 3 (Day 30±3),
Visit 4 (Day 60±3) and
Visit 5 (Day 90±3). 
 
Secondary Outcome  
Outcome  TimePoints 
Reduction in the size of the endometrioma as calculated by the Ultrasound sonography (USG) from baseline to end of the study.  At Screening Visit (Visit 1) and
Visit 5 (Day 90±3). 
Consumption of rescue pain medication for endometriosis associated pelvic pain from baseline to end of the study.  At Visit 3 (Day 30±3),
Visit 4 (Day 60±3) and
Visit 5 (Day 90±3). 
Mean change in the serum vascular endothelial growth factor (VEGF) from baseline to end of the study.  At Screening Visit (Visit 1) and
Visit 5 (Day 90±3). 
Changes in the health-related quality of life using the HRQoL-4 questionnaire from baseline to end of the study.  At Visit 2 (Day 1 / Baseline),
Visit 3 (Day 30±3),
Visit 4 (Day 60±3) and
Visit 5 (Day 90±3). 
Adverse events / serious adverse events reported during the study.  Throughout the study. 
Changes in clinical laboratory parameters from screening to end of the study visit.  At Screening Visit (Visit 1) and
Visit 5 (Day 90±3). 
 
Target Sample Size   Total Sample Size="228"
Sample Size from India="228" 
Final Enrollment numbers achieved (Total)= "228"
Final Enrollment numbers achieved (India)="228" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   03/04/2023 
Date of Study Completion (India) 11/10/2023 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   NIL 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

This trial is a phase III, randomized, double blind, single dummy, active controlled, prospective, parallel group, comparative, multicentric clinical study to evaluate the efficacy, safety and tolerability of Dydrogesterone Sustained Release Tablets 30 mg versus Dydrogesterone Tablets 10 mg for the treatment of endometriosis in women.

 

Patients who are willing and able to participate in the study will sign and date the Informed Consent Form on the day of screening visit (Visit 1). During this screening period, patients who are willing to give consent will be evaluated for all the eligibility criteria. Eligible patients (female) aged 18 to 45 years (both inclusive), diagnosed with endometriosis based on imaging studies i.e., USG and endometriosis associated pelvic pain having a score of at least 30 mm on a 100 mm visual analog scale at screening visit will be considered for the study.

 

After confirming the inclusion/exclusion criteria the subject will be randomized and provided with study medication at randomization visit. Subjects will be provided with patient diary at randomization visit, which need to be brought along with in each subsequent visit till the last visit. Follow up visits will be done on day 30(±3), day 60(±3) and day 90(±3) (final visit) of treatment to assess efficacy, safety and tolerability.

 

Patients will be assigned to either of the two arms i.e., Arm A or Arm B consisting of Dydrogesterone Sustained Release Tablets 30 mg & Placebo Tablets or Dydrogesterone Tablets 10 mg.

 

Patients will be advised to take one tablet thrice a day orally, swallowed with water in the morning, afternoon and evening around same time every day for 90 days.

 

Test Product

Dydrogesterone Sustained Release Tablets 30 mg & Placebo Tablets

Morning - One tablet of test product

Afternoon - One tablet of placebo matching test product

Evening - One tablet of placebo matching test product

 

Reference Product

Dydrogesterone Tablets 10 mg

Morning - One tablet of reference product

Afternoon - One tablet of reference product

Evening - One tablet of reference product

 
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