| CTRI Number |
CTRI/2016/06/007034 [Registered on: 23/06/2016] Trial Registered Prospectively |
| Last Modified On: |
14/07/2016 |
| Post Graduate Thesis |
No |
| Type of Trial |
BA/BE |
|
Type of Study
|
|
| Study Design |
Randomized, Crossover Trial |
|
Public Title of Study
|
To compare bioavailibility of Methotrexate Tablets 2.5 mg( Amneal pharmaceuticals) with Methotrexate
Tablets USP 2.5 mg (DAVA Pharmaceuticals, Inc.USA) in patients with mild to severe psoriasis
or rheumatoid arthritis |
|
Scientific Title of Study
|
A multicenter, randomized, open label, two treatment, two
period, two sequence, single-dose, two-way, crossover, bioequivalence study of Methotrexate Tablets USP, 2.5 mg manufactured by Amneal Pharmaceuticals, with
Methotrexate Tablets USP 2.5 mg Manufactured for DAVA
Pharmaceuticals, Inc., Fort Lee, NJ 07024 USA in patients
with mild to severe psoriasis or rheumatoid arthritis, who are already on established regimens of 2.5 mg every 12 hours under fasting condition. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 15-VIN-515 Version 1.0 dated 24th July 2015 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Prayag Shah |
| Designation |
General Manager |
| Affiliation |
Amneal Pharmaceuticals Pvt. Ltd. |
| Address |
508-514, 5th floor, Amneal Pharmaceuyticals, Corporate office, Venus Atlantis, Nr. Safal Pegasus, Prahladnagar, Ahmedabad
508-514, 5th floor, Amneal Pharmaceuyticals, Corporate office, Venus Atlantis, Nr. Safal Pegasus, Prahladnagar, Ahmedabad
Ahmadabad
GUJARAT
380015
India |
| Phone |
8128671400 |
| Fax |
07967778303 |
| Email |
dr.prayag@amneal.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Prayag Shah |
| Designation |
General Manager |
| Affiliation |
Amneal Pharmaceuticals Pvt. Ltd. |
| Address |
508-514, 5th floor, Amneal Pharmaceuyticals, Corporate office, Venus Atlantis, Nr. Safal Pegasus, Prahladnagar, Ahmedabad
508-514, 5th floor, Amneal Pharmaceuyticals, Corporate office, Venus Atlantis, Nr. Safal Pegasus, Prahladnagar, Ahmedabad
GUJARAT
380015
India |
| Phone |
8128671400 |
| Fax |
07967778303 |
| Email |
dr.prayag@amneal.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Prayag Shah |
| Designation |
General Manager |
| Affiliation |
Amneal Pharmaceuticals Pvt. Ltd. |
| Address |
508-514, 5th floor, Amneal Pharmaceuyticals, Corporate office, Venus Atlantis, Nr. Safal Pegasus, Prahladnagar, Ahmedabad
508-514, 5th floor, Amneal Pharmaceuyticals, Corporate office, Venus Atlantis, Nr. Safal Pegasus, Prahladnagar, Ahmedabad
GUJARAT
380015
India |
| Phone |
8128671400 |
| Fax |
07967778303 |
| Email |
dr.prayag@amneal.com |
|
|
Source of Monetary or Material Support
|
| Amneal Pharmaceuticals, USA
85, adams avenue, happauge, NY11788, USA |
|
|
Primary Sponsor
|
| Name |
Amneal Pharmaceuticals USA |
| Address |
Amneal Pharmaceuticals
85, Adams Avenue, Hauppauge, NY 11788, USA
|
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Accutest Research Laboratories I PVt Ltd |
Opp. The Grand Bhagwati,
S.G. Highway,
Bodakdev, Ahmedabad - 380 059,
Gujarat, India. |
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 3 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Saurabh Kapadia |
Kanoria Hospital & Research Centre |
Airport Gandhinagar Highway, Village Bhat,
Gandhinagar – 382 428, Gujarat, India
Gandhinagar
GUJARAT |
9824261031
drsaurabhkapadia@yahoo.com |
| Dr Smita Nagpal |
Savior Multispeciality Hospital |
Near Bharat Petrol Pump, Near Lakhudi Talav, Stadium Road, Navrangpura, Ahmedabad 380014, India
Ahmadabad
GUJARAT |
9825721525
nagpalsmita@gmail.com |
| Dr Piyush Joshi |
Sterling Hospital |
Sterling hospital Road, Memnagar, Ahmedabad, Gujarat, India - 380052
Ahmadabad
GUJARAT |
8879102056
pnjoshi2005@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 3 |
| Name of Committee |
Approval Status |
| Kanoria ethics committee |
Approved |
| Saviour Hospital Ethics Committee situated at Near Bharat Petrol Pump, Near Lakhudi Talav, Stadium Road, Navrangpura, Ahmedabad 380014 India |
Approved |
| Sterling Hospital Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Patients with mild to severe psoriasis or rheumatoid arthritis, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Methotrexate Tablets USP 2.5 mg (DAVA Pharmaceuticals ) |
On day 1 of each period, each patient would receive their dose of Methotrexate 2.5 using either the test or reference product in a crossover design. Two subsequent doses will be of locally approved drug at every 12 hrs of interval after the administration of study drug on day 1. |
| Intervention |
Methotrexate Tablets USP, 2.5 mg (Amneal Pharmaceuticals) |
On day 1 of each period, each patient would receive their dose of Methotrexate 2.5 using either the test or reference product in a crossover design. Two subsequent doses will be of locally approved drug at every 12 hrs of interval after the administration of study drug on day 1. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1. Men or Women, between 18 to 65 years of age (both inclusive).
2. Ability to provide informed consent prior to participation in the study
3. Patients with mild to severe psoriasis or rheumatoid arthritis, who are already on established regimens of 2.5 mg every 12 hours (7.5 mg per week in three divided doses).
4. Confirmed diagnosis of psoriasis by clinical examination or after dermatologic consultation.
or
Confirmed diagnosis of mild to severe rheumatoid arthritis based on at least 1 of the following:
i. Documented history of positive rheumatoid factor
ii. Current presence of rheumatoid factor
iii. Radiographic erosion within 12 months prior to enrollment
iv. Presence of serum anti-cyclic citrullinated peptide antibodies (anti-CCP).
5. Women of childbearing potential (except for those who have completed one year since menopause or have gone through hysterectomy or bilateral tubal ligation within past 6 months) must have a negative serum pregnancy test at screening and negative urine pregnancy test on check in to housing, and must agree to use an adequate method of contraception.
6. Patient’s screening laboratory assessment (complete blood count [CBC] and blood chemistries) are clinically non-significant as per the discretion of the Investigator.
7. No history of addiction to any recreational drug or drug dependence.
8. No participation in any clinical study within the past 60 days prior to receiving the first dose of investigational product for the current study. |
|
| ExclusionCriteria |
| Details |
1.A history of allergic or adverse reactions to Methotrexate Sodium or any related drug or any excipient of methotrexate tablets.
2.Male or female of childbearing potential unwilling to use barrier contraceptive precautions throughout the trial and at least for 3 months (for males) and for at least one ovulatory cycle (for females) after last dose of study medication.
3.Patients with alcoholism, alcoholic liver disease or other chronic liver disease.
4.Patients who are diagnosed to be HIV or Hepatitis B or Hepatitis C Virus reactive/positive.
5.Patients who have clinically significant abnormal laboratory values at screening.
6.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 except study indication.
7.Patients who have overt or laboratory evidence of immunodeficiency syndromes.
8.Patients currently suffering from or having a history of malignant lymphoma or tumor lysis syndrome.
9.Patients who have pre-existing hematopoietic impairment/ blood dyscrasias, such as bone marrow hypoplasia, aplastic anemia, pancytopenia, leukopenia, neutropenia, thrombocytopenia and or significant anemia.
10.Patient with lymphadenopathy and lymphoproliferative disorders.
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To characterize the pharmacokinetic profile of Methotrexate Tablets USP, 2.5 mg of Amneal Pharmaceuticals, compared to that of the Methotrexate Tablets USP 2.5 mg manufactured for DAVA Pharmaceuticals, Inc., Fort Lee, NJ 07024 USA in patients with mild to severe psoriasis or rheumatoid arthritis, who are already on established regimens of 2.5 mg every 12 hours for three doses per week under fasting conditions, and to assess their bioequivalence. |
The pre-dose blood sample (00.00) will be collected within 5 minutes before dosing on Day 1 of each period. On day 1, the post-dose blood samples will be drawn at 0.167, 0.333,
0.500, 0.750, 1.000, 1.250, 1.500, 1.750, 2.000, 2.333, 2.667, 3.000, 3.500, 4.000, 4.500, 5.000, 6.000, 7.000, 8.000, 10.000 and 12.000 following drug administration in each
period. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| To monitor the adverse events and to ensure the safety of Patient |
NA |
|
|
Target Sample Size
|
Total Sample Size="48"
Sample Size from India="48"
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)
|
30/06/2016 |
| 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="3"
Days="5" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
NA |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
To compare and evaluate the bioequivalence study of Methotrexate Tablets 2.5 mg (manufactured by Amneal Pharmaceuticals) with Methotrexate
Tablets USP 2.5 mg (DAVA Pharmaceuticals, Inc.,Fort Lee, NJ 07024 USA)
in patients with mild to severe psoriasis or rheumatoid arthritis (RA),
who are already on established regimens of 2.5 mg every 12 hours under
fasting condition. Total expected duration of the study will be of at
least 8 days from the day of admission of the first period till the end
of study sample collection in period II. There will be at least 7 days
duration between the IMP administrations in two study periods. After IMP
administration in each period (on day 1), patients will be advised to
receive their scheduled dose of 2.5 mg Methotrexate
tablet 12 hours apart for additional 2 doses using locally approved
drug. A total of 22 PK samples will be collected during each period. |