BE Study in Patients - Methotrexate Tablets

NCT02940561 | Unknown Phase 1 DMC

• 1 other identifier: 15-VIN-515
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 3

Brief Summary

To characterize the pharmacokinetic profile of the Test product - Methotrexate Tablets USP, 2.5 mg of Amneal Pharmaceuticals, compared to that of the corresponding Reference product - Methotrexate Tablets USP 2.5 mg manufactured for DAVA Pharmaceuticals, Inc. 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.

Conditions

Psoriasis; Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (2)

• Area Under the Curve (AUC0-12)

  The area under the plasma concentration versus time curve, from time 0 to 12 hours post-dose, calculated using linear trapezoidal method. It will be calculated using plasma concentration vs. time profile (Actual time of sample collection) data of the investigational products in individual subjects.

  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

• Maximum Plasma Concentration (Cmax)

  Maximum measured plasma concentration over the time span specified. It will be calculated using plasma concentration vs. time profile (Actual time of sample collection) data of the investigational products in individual subjects.

  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 Outcomes (1)

• Safety Parameters

  through study completion, approximately 23 days

Study Arms (2)

Methotrexate - Amneal

EXPERIMENTAL

Methotrexate Tablets USP, 2.5 mg, single-dose in each period

Drug: Methotrexate - Amneal

Methotrexate - DAVA

ACTIVE COMPARATOR

Methotrexate Tablets USP, 2.5 mg, single-dose in each period

Drug: Methotrexate - DAVA

Interventions

Methotrexate - Amneal DRUG

Methotrexate Tablets, USP contain an amount of methotrexate sodium equivalent to 2.5 mg of methotrexate, USP and are round, biconvex, yellow tablets, scored in half on one side, engraved with "A" above the score and "1" below

Also known as: Methotrexate Sodium

Methotrexate - Amneal

Methotrexate - DAVA DRUG

Methotrexate Tablets, USP contain an amount of methotrexate sodium equivalent to 2.5 mg of methotrexate and are round, convex, yellow tablets, scored in half on one side, engraved with M above the score, and 1 below

Also known as: Methotrexate Sodium

Methotrexate - DAVA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amneal Pharmaceuticals, LLC: lead
• Accutest Research Laboratories (I) Pvt. Ltd.: collaborator

Study Sites (3)

Saviour Hospital

Ahmedabad, Gujarat, 380009, India

RECRUITING

Sterling Hospital

Ahmedabad, Gujarat, 380052, India

RECRUITING

Kanoria Hospital

Gandhinagar, Gujurat, 382428, India

RECRUITING

MeSH Terms

Conditions

Psoriasis; Arthritis, Rheumatoid

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Prayag N Shah, MD

  Amneal Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Prayag N Shah, MD

CONTACT

+91 8128671400; Dr.Prayag@amneal.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2016
• First Posted: October 21, 2016
• Study Start: August 1, 2016
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: October 21, 2016

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will not share

Locations

IN (3)