| CTRI Number |
CTRI/2014/05/004641 [Registered on: 29/05/2014] Trial Registered Retrospectively |
| Last Modified On: |
18/08/2014 |
| 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 / Imeth® in Patients with Rheumatoid Arthritis under fasting condition. |
|
Scientific Title of Study
|
A randomized, balanced, multi-centre, open-label, single dose, two-treatment, two-period, two-sequence, crossover comparative bioavailability study of test Methotrexate (as Methotrexate Sodium) 3 x 5 mg modified-immediate release capsules (from Disphar International B.V., The Netherlands), with reference Imeth® 6 x 2.5 mg (methotrexate 15 mg) immediate release tablets (from Orion Pharma, Finland), in 16 adult patients with rheumatoid arthritis under fasting condition. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| RLS/1213/053, Version 01 dated 27th Feb 2014 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Prashant Pandya |
| Designation |
General Manager- Clinical Development |
| Affiliation |
Reliance Life Sciences Pvt.Ltd |
| Address |
Dhirubhai Ambani Life Sciences Centre R-282 TTC Area of MIDC Rabale Mumbai Maharashtra
Thane
MAHARASHTRA
400701
India |
| Phone |
02240678236 |
| Fax |
02240678299 |
| Email |
Prashant.Pandya@Relbio.Com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Prashant Pandya |
| Designation |
General Manager- Clinical Development |
| Affiliation |
Reliance Life Sciences Pvt.Ltd |
| Address |
Dhirubhai Ambani Life Sciences Centre R-282 TTC Area of MIDC Rabale Mumbai Maharashtra
Thane
MAHARASHTRA
400701
India |
| Phone |
02240678236 |
| Fax |
02240678299 |
| Email |
Prashant.Pandya@Relbio.Com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Prashant Pandya |
| Designation |
General Manager- Clinical Development |
| Affiliation |
Reliance Life Sciences Pvt.Ltd |
| Address |
Dhirubhai Ambani Life Sciences Centre R-282 TTC Area of MIDC Rabale Mumbai Maharashtra
Thane
MAHARASHTRA
400701
India |
| Phone |
02240678236 |
| Fax |
02240678299 |
| Email |
Prashant.Pandya@Relbio.Com |
|
|
Source of Monetary or Material Support
|
| Reliance Life Sciences Pvt. Ltd.
Dhirubhai Ambani Life Sciences Centre,
Plot R-282 TTC Area of MIDC, Rabale, Navi Mumbai 400 701 India.
|
|
|
Primary Sponsor
|
| Name |
Disphar International BV |
| Address |
Tolweg 15, 3741 LM Baarn
The Netherlands
PO Box 17, 3740 AA Baarn
The Netherlands
Winkelskamp 6, 7255 PZ Hengelo (Gld)
The Netherlands
|
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 2 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Girishchandra Baratakke |
BJGMJ and Sasson General Hospital |
Professor and HOD, Department of Orthopedic, B.J. Govt. Medical College & Sassoon General Hospital Pune -411001,Maharashtra, India
Pune
MAHARASHTRA |
09422036065
02026128000
girishbartakke@rediffmail.com |
| Dr Shailaja Girish Bhatia |
Medipoint Hospital Pvt. Ltd. |
Consultant Physician, Department of Medicine, Medipoint Hospital Pvt Ltd, 241/1 New D.P Road, Aundh, Pune – 411007, Maharashtra, India
Pune
MAHARASHTRA |
09527016688
02027298081
shailajagbhatia@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 2 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee of B.J. Government Medical college and Sasoon General Hospital. |
Approved |
| Penta-med Ethics committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
rheumatoid arthritis , |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Reference - Imeth® 6 x 2.5 mg (methotrexate 15 mg) immediate release tablets |
NIL |
| Intervention |
Test- Methotrexate (as Methotrexate Sodium) 3 x 5 mg modified-immediate release capsules. |
NIL |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
50.00 Year(s) |
| Gender |
Both |
| Details |
Inclusion Criteria
1. Adult patients suffering from rheumatoid arthritis; aged between 18 to 50 years (both inclusive)
2. Patients should already be receiving oral methotrexate 15 mg once weekly for rheumatoid arthritis.
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 β-HCG pregnancy test at screening or positive urine pregnancy 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 post-study follow-up (i.e. 7 days after the last dosing in Period II). Female patients using hormonal contraceptives either oral or implants.
4. Subjects that intend to father a child during treatment and up to 6 months afterwards.
5. Female patients with history of dysmenorrhea requiring medication
6. Patients with inadequate venous access in their left or right arm to allow the collection of all samples via venous cannula in the study
7. 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.
8. 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.
9. Any treatment which could affect the pharmacokinetic of methotrexate (salicylates, hypoglycaemics, diuretics, sulphonamides, diphenylhydantoins, tetracyclines, chloramphenicol and p-aminobenzoic acid, probenecid, penicillins, Chloroquine, omeprazole, etretinate, co-trimoxazole and trimethoprim etc.) administered within 1 month of starting of study/in past 1 month.
10. Patients with history of drug hyper sensitivity to methotrexate or related drugs or to any of the excipient of the formulation
11. 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).
12. Patients who are diagnosed to be HIV 1 and 2 or Hepatitis B (HBsAg) or Hepatitis C (HCV) virus reactive/positive.
13. Patients with clinically significant abnormal haemoglobin (Hb), total white blood cells count (WBC), differential WBC count, platelet count and hematocrit
14. 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.
15. 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)
16. Patients with clinically significant abnormal results during ultrasonographic examinations.
17. 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
18. 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
|
Centralized |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
Bioavailability of the both the formulations (T vs R) will be assessed in relation to the
primary pharmacokinetic parameters for methotrexate:
ï‚•ï€ Cmax
ï‚•ï€ AUC(0-t)
|
D15 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
To monitor safety parameters for all the investigational products by performing the clinical
and laboratory examinations and recording adverse events during the study.
To determine and compare secondary pharmacokinetic parameters of test and reference
products for methotrexate, i.e.
AUC0—∞
ï‚•ï€ tmax
ï‚•ï€ Kel
ï‚•ï€ t1/2
ï‚•ï€ AUCres
ï‚•ï€ Intra & inter-subject variability
|
D15 |
|
|
Target Sample Size
|
Total Sample Size="16"
Sample Size from India="16"
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)
|
30/04/2014 |
| 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="0"
Days="16" |
|
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 compare bioavailability of test Methotrexate (as Methotrexate Sodium) 3 x 5 mg modified-immediate release capsules (from Disphar International B.V., The Netherlands), with reference Imeth® 6 x 2.5 mg (methotrexate 15 mg) immediate release tablets (Orion Pharma, Finland) in 16 adult patients with rheumatoid arthritis under fasting condition |