BE Study in Patients - Methotrexate Tablets

• Register: ClinicalTrials.gov
• Last refreshed on: 31 October 2016
• Main ID: NCT02940561
• Date of registration: 15/09/2016
• Prospective Registration: No
• Primary sponsor: Amneal Pharmaceuticals, LLC
• Public title: BE Study in Patients - Methotrexate Tablets
• Scientific title: 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.
• Date of first enrolment: August 2016
• Target sample size: 48
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT02940561
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label
• Phase: Phase 1

Countries of recruitment

India

Contacts

• Name: Prayag N Shah, MD
• Affiliation: Amneal Pharmaceuticals

• Name: Prayag N Shah, MD

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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)

- Confirmed diagnosis of psoriasis by clinical examination or after dermatologic
consultation.

or confirmed diagnosis of mild to severe rheumatoidarthritis 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).

- Women of childbearing potential (include girls who have entered puberty and all women
who have a uterus and ovaries and have not completed menopause wherein menopause is
the permanent end of menstruation and fertility. Females who have 12 consecutive
months of spontaneous amenorrhea (not induced by a medical condition or medical
therapy) or have bilateral absence of ovaries (surgical or congenital) have completed
menopause 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.

- Patient's screening laboratory assessment (complete blood count [CBC] and blood
chemistries) are clinically non-significant as per the discretion of the
Investigator.

- No history of addiction to any recreational drug or drug dependence.

- No participation in any clinical study within the past 60 days prior to receiving the
first dose of investigational product for the current study.

Exclusion Criteria:

- A history of allergic or adverse reactions to Methotrexate Sodium or any related drug
or any excipient of methotrexate tablets.

- Females of childbearing potential unwilling to use adequate contraception (as defined
in the protocol) throughout the trial and for one month after the last dose of study
medication.

- Males unwilling to use a male condom throughout the trial and for three months after
the last dose of study medication

- Patients with alcoholism, alcoholic liver disease or other chronic liver disease.

- Patients who are diagnosed to be HIV or Hepatitis B (HBsAg) or Hepatitis C (HCV)
virus reactive/positive.

- Patients who have clinically significant abnormal laboratory values at screening.

- 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.

- Patients who have overt or laboratory evidence of immunodeficiency syndromes.

- Patients currently suffering from or having a history of malignant lymphoma or tumor
lysis syndrome.

- Patients who have pre-existing hematopoietic impairment/ blood dyscrasias, such as
bone marrow hypoplasia, aplastic anemia, pancytopenia, leukopenia, neutropenia,
thrombocytopenia and or significant anemia.

- Patient with lymphadenopathy and lymphoproliferative disorders.

- Patients suffering from any acute infection within two weeks prior to randomization.

- Patients with a clinically significant past history or current medical condition of:
Pulmonary disorders (Pneumonia, COPD and asthma), pleural effusions, Cardiovascular
disorders (especially cardiac blocks, pericarditis, pericardial effusion, hypotension
and thromboembolic events ), Neurological disorders (especially seizures, migraines),
Gastrointestinal tract disorders including a history or presence of significant
gastric and/or duodenal ulceration and bleeding, hematemesis, melena, enteritis,
pancreatitis, Renal and/or hepatic disorders, Coagulation disorders, Patient with
ascites, Patient with uncontrolled diabetes mellitus.

- Female patients who are pregnant or breastfeeding

- History or presence of cancer.

- Evidence of any significant uncontrolled concomitant disease which in the
investigator's opinion would exclude the patient participation.

- Expected changes in concomitant medications during the period of study.

- Tested positive for Alcohol breath or Urine drug of abuse.

- Any treatment which could affect the pharmacokinetic of methotrexate (NSAIDs,
salicylates, hypoglycemics, 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.

- Patient had major surgery within 4 weeks prior to study entry, or who have not
recovered from prior major surgery.

- Patients with any significant history of non-compliance to medical regimens or with
inability to grant a reliable informed consent.

- History of difficulty with donating blood or difficulty in accessibility of veins.

- Patients for whom oral administration of drug is not possible.

- An unusual or abnormal diet, for whatever reason e.g. religious fasting.

- Blood donation/ loss exceeding 200 ml within last 60 days prior to receiving the
first dose of investigational product for the current study.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Psoriasis

Rheumatoid Arthritis

Intervention(s)

Drug: Methotrexate - Amneal

Drug: Methotrexate - DAVA

Primary Outcome(s)

Maximum Plasma Concentration (Cmax) [Time Frame: Blood samples will be collected on day 1 of each period, pre-dose and post-dose 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 and 4 hours]

Area Under the Curve (AUC0-12) [Time Frame: Blood samples will be collected on day 1 of each period, pre-dose and post-dose 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, and 4 hours]

Secondary Outcome(s)

Safety Parameters [Time Frame: through study completion, approximately 23 days]

Secondary ID(s)

15-VIN-515

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Accutest Research Laboratories (I) Pvt. Ltd.