| CTRI Number |
CTRI/2015/02/005506 [Registered on: 06/02/2015] Trial Registered Retrospectively |
| Last Modified On: |
23/02/2015 |
| Post Graduate Thesis |
No |
| Type of Trial |
BA/BE |
|
Type of Study
|
|
| Study Design |
Randomized, Crossover Trial |
|
Public Title of Study
|
A clinical trial to study the effects of two drugs, Methotrexate tablets USP 2.5 mg / Rheumatrex® in Patients with suffering from psoriasis. |
|
Scientific Title of Study
|
A randomized, multicentric, open-label, single dose, two-treatment, two-sequence, two-period, crossover, bioequivalence study of test Methotrexate tablets USP 2.5 mg (from Zhejiang Hisun Pharma Co. Ltd., China) with reference Rheumatrex® (methotrexate tablets USP) 2.5 mg of Dava Pharmaceuticals, Inc., USA in 42 adult, patients suffering from psoriasis under fasting condition. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| RLS/1113/052, version 1.0, 27th feb 2014 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Pravin Ghadge |
| Designation |
Head-Medical writing &Pharmacovigiliance |
| Affiliation |
Reliance Life Sciences Pvt.Ltd |
| Address |
Dhirubhai Ambani Life Sciences Centre R-282 TTC Area of MIDC Rabale Mumbai
Mumbai
MAHARASHTRA
400701
India |
| Phone |
022-67678431 |
| Fax |
022-40678299 |
| Email |
pravin.ghadge@relbio.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Pravin Ghadge |
| Designation |
Head-Medical writing &Pharmacovigiliance |
| Affiliation |
Reliance Life Sciences Pvt.Ltd |
| Address |
Dhirubhai Ambani Life Sciences Centre R-282 TTC Area of MIDC Rabale Mumbai
Mumbai
MAHARASHTRA
400701
India |
| Phone |
022-67678431 |
| Fax |
022-40678299 |
| Email |
pravin.ghadge@relbio.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Sanjeev Hegde |
| Designation |
Head- Clinical Development |
| Affiliation |
Reliance Life Sciences Pvt.Ltd |
| Address |
Dhirubhai Ambani Life Sciences Centre R-282 TTC Area of MIDC Rabale Mumbai
Mumbai
MAHARASHTRA
400701
India |
| Phone |
02267678208 |
| Fax |
022-40678299 |
| Email |
sanjeev.hegde@relbio.com |
|
|
Source of Monetary or Material Support
|
| Zhejiang Hisun Pharma Co. Ltd.,
46 Waisha Road,
Jiaojiang, Taizhou,
Zhejiang, China 318000
|
|
|
Primary Sponsor
|
| Name |
Zhejiang Hisun Pharma Co Ltd |
| Address |
46 Waisha Road,
Jiaojiang, Taizhou,
Zhejiang, China 318000
|
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 5 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Pramod Kumar |
Kasturba Medical College Hospital |
Department of Skin and STD, 1st Floor, Room No 10, Kasturba Medical College Hospital, Attavar, Mangalore 575001
Dakshina Kannada
KARNATAKA |
9845164946
pkderm@hotmail.com |
| DrLeelavathyB |
Life Care Hospital |
Department of Dermatology, New no 99, Old no 23/24, Om Complex, 20th Main, Gangothri Circle, BTM 1st stage, Bangalore
Bangalore
KARNATAKA |
9448169982
drleelaskincare@rediffmail.com |
| Dr Hemant Talnikar |
Medipoint Hospital Pvt. Ltd. |
Aster Medipoint Hospital, 1st Floor, 241/1 New D.P. Road, Aundh Pune-411007,
Pune
MAHARASHTRA |
9422087726
talanikarh@gmail.com |
| Dr G Manmohan |
Osmania General Hospital |
Department of Dermatology, Ground Floor, Osmania General Hospital, Afjalganj, Hyderabad - 500012
Hyderabad
ANDHRA PRADESH |
9246539527
manmohan.5777@gmail.com |
| Dr Parag Gopal Kalyani |
Ruby Hall Clinic |
Department of Dermatology, Ground Floor, Ruby Hall Clinic, 40 Sassoon Road, Pune 411001
Pune
MAHARASHTRA |
9822284447
parag.kalyani@yahoo.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 5 |
| Name of Committee |
Approval Status |
| Ethics Committee Life Care Hospital |
Approved |
| Ethics COmmittee Osmania Medical College |
Approved |
| Institutional Ethics Committee, Poona Medical Research Foundation |
Approved |
| Manipal University Ethics Committee |
Approved |
| Penta-med Ethics committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Adult patients suffering from psoriasis, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Methotrexate tablets USP 2.5 mg |
Frequency duration: Single dose of test drug and single dose of reference drug will be given (as per randomization sequence) during the entire study
Route of administration: Oral
|
| Comparator Agent |
Rheumatrex® (Methotrexate tablets USP) 2.5 mg |
Frequency duration: Single dose of test drug and single dose of reference drug will be given (as per randomization sequence) during the entire study
Route of administration: Oral
|
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
45.00 Year(s) |
| Gender |
Both |
| Details |
1. Adult patients suffering from psoriasis; aged between 18 to 45 years (both inclusive)
2. Patients should already be receiving 2.5 mg 12 hourly of oral methotrexate with weekly dose is in the range of 5-10.0 mg for psoriasis
3. Patients willing to voluntarily provide written informed consent.
4. Patients willing to undergo pre and post-study physical examinations and laboratory investigations.
5. Patients willing to adhere to protocol and they should not consume coffee, tea, chocolate, grape fruit juice or soft drink at least 24 hours prior to investigational product administration (i.e. in house monitoring and the remaining based on history) and during their clinical stay in each study period.
6. Patient should be willing to adhere to the protocol and they should not consume alcohol at least 48 hours prior to dosing (i.e. in-house monitoring and the remaining based on history) and should agree not to take any amount of alcohol during the study period.
|
|
| ExclusionCriteria |
| Details |
1. Patients incapable of understanding the informed consent process.
2. Pregnant [female patients with a positive pregnancy test at screening or positive serum β-HCG test (done at Check-in of each study period)] or lactating females
3. Female patients of childbearing potential who is unwilling or unable to use an appropriate method of contraception, at least 14 days prior to the first dose of study medication until the poststudy follow-up (i.e. 7 days after the last dosing in Period II). Female patients using hormonal contraceptives either oral or implants.
4. Female patients with history of dysmenorrhea requiring medication
5. Patients with inadequate venous access in their left or right arm to allow the collection of all samples via venous cannula in the study
6. Patients with evidence of psychiatric disorder likely to limit the validity of consent to participate in the study, or limit the ability to comply with the protocol requirements.
7. Patients with any evidence of organ dysfunction or any clinically significant deviation from normal in their physical or clinical evaluation including ECG and X-ray results.
8. Any treatment which could affect the pharmacokinetic of methotrexate (salicylates, hypoglycaemics, diuretics, sulphonamides, diphenylhydantoins, tetracyclines, chloramphenicol and p-aminobenzoic acid, the acidic anti-inflammatory agents, probenecid, penicillins, Chloroquine, omeprazole, etretinate, co-trimoxazole and trimethoprim etc.) administered within 1 month of starting of study/in past 1 month.
9. Patients with history of drug hyper sensitivity to methotrexate or related drugs or to any of the excipient of the formulation
10. Patients with a history of alcohol, found with current alcohol abuse based on Alcohol breath test and with history of drug abuse, found urinary screen test positive for drugs of abuse (Amphetamines, Morphine, Benzodiazepines, Marijuana, Cocaine and Barbiturates).
11. Patients who are diagnosed to be HIV 1 and 2 or Hepatitis B (HBsAg) or Hepatitis C (HCV) virus reactive/positive.
12. Patients with clinically significant abnormal haemoglobin (Hb), total white blood cells count (WBC), differential WBC count, platelet count and hematocrit
13. Patients who, have clinically significant abnormal laboratory values for serum creatinine, blood urea nitrogen, (BUN), serum aspartate aminotransferase (AST), serum alanine aminotransferase
(ALT), serum alkaline phosphatase (ALP), c-glutamyltranspeptidase, serum bilirubin, serum glucose (fasting) etc.
14. Patients with clinically significant abnormal urine analysis, defined as the presence of RBC (5/HPF), pus cells (5/HPF), epithelial cells (5/HPF), glucose (positive), ketones (positive), bilirubin (positive) and protein (positive)
15. Patients with clinically significant abnormal results during ultrasonographic examinations.
16. Patients with a clinically significant past history or current medical condition of:
• Pulmonary disorders (COPD and asthma)
• Cardiovascular disorders (especially cardiac blocks)
• Neurological disorders (especially seizures, migraine)
• GIT disorders including history or presence of significant gastric and/or duodenal ulceration
• Renal and/or hepatic disorders
• Coagulation disorders
• Endocrine disorders (especially diabetes mellitus)
• History or presence of cancer
17. Patients who have participated in any other clinical investigation or have bled more than 300 ml in the past 3 months.
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
To establish the bioequivalence of test Methotrexate tablets USP 2.5 mg (from Zhejiang Hisun Pharma Co. Ltd., China) with reference RheumatrexR (methotrexate tablets USP) 2.5 mg of Dava Pharmaceuticals, Inc., USA.
Bioequivalence of the two formulations (T vs R) in relation to the:
o Cmax,
o AUC0—t
o AUC0-∞
|
Bioequivalence of the two formulations Test vs Reference in relation to the:
• Rate of absorption
• Extent of absorption
|
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
To monitor all the adverse events, including laboratory parameters
2. To determine other pharmacokinetic parameters of test and reference products
o Tmax,
o Kel
o t1/2
o Tlag - lag time
o AUC_%Extrap_obs
o λz
|
1. To monitor safety
• Adverse events
• Laboratory abnormalities
2. Assessment of the pharmacokinetic parameters
|
|
|
Target Sample Size
|
Total Sample Size="42"
Sample Size from India="42"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
16/12/2014 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="0"
Months="6"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
|
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
The present study aims to establish bioequivalence of Methotrexate tablets USP 2.5 mg (from Zhejiang Hisun Pharma Co. Ltd., China) with reference RheumatrexR (methotrexate tablets USP) 2.5 mg of Dava Pharmaceuticals, Inc., USA. Methotrexate 2.5 mg at 12-hour intervals for three doses weekly is also recommended dose in the treatment of psoriasis. The protocol is designed for product submission to US FDA. The US FDA OGD has recommended single dose bioequivalence study with methotrexate 2.5 mg strength in psoriasis patients. |