PsoriasisPhase 1NCT02940561
BE Study in Patients - Methotrexate Tablets
A Phase 1 study testing Methotrexate - Amneal and Methotrexate - DAVA in people with Psoriasis and Rheumatoid Arthritis, run by Amneal Pharmaceuticals, LLC at 3 sites in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Psoriasis, Rheumatoid Arthritis
- What is being tested?
- Methotrexate - Amneal and Methotrexate - DAVA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 3 sitesIndia
- Study dates
- Aug 2016to Oct 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country.
India3 sites, 3 recruiting
- Recruiting
Saviour Hospital
Ahmedabad, Gujarat, 380009
Smita Nagpal, MD, 9825721525, nagpalsmita@gmail.com
Smita Nagpal, MD
- Recruiting
Sterling Hospital
Ahmedabad, Gujarat, 380052
Piyush Joshi, MD, +91 8879102056, pnjoshi2005@gmail.com
Piyush Joshi, MD
- Recruiting
Kanoria Hospital
Gandhinagar, Gujurat, 382428
Saurabh Kapadia, MD, +91-9824261031, drsaurabhkapadia@yahoo.com
Saurabh Kapadia, MD
About this study
Official 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.
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.
Read the detailed description
Patients will continue their own established dose of 2.5 mg tablet at 12 hours intervals for 3 doses given as a course once weekly. This dosing regimen will be kept constant throughout the study period.
On day 0 of each period, the patient will be hospitalized/ housed in the clinical facility/hospital, so patient will be administered IP dose on day 1 under supervision of trained study staff.
In supervised dosing, patient will be administered oral dose of Methotrexate Tablet 2.5 mg (Test or Reference product as per randomization schedule) with approximately 240 mL of water at ambient temperature in sitting position. Mouth check will be done by investigator/ designee followed by IP administration to verify dosing compliance.
The patient will be advised to take two subsequent doses of the locally approved drug at every 12 hours of interval after the administration of study drug on day 1.
Compliance to subsequent two doses of locally approved Methotrexate tablets 2.5 mg will be ensured as below in each period.
The dose which is to be given 12 hours after IP administration (Second dose) will be administered inside clinical facility after collection of 12 hours post-dose PK sample under supervision of trained study personnel. The next dose (third dose) will be provided to the patients with the instruction to take the same on their own. Telephonic follow-up will be made on the next day for this third dose. The same will be documented in the patient dosing log.
In period I, patient will be housed on day 0 at least 12 hours prior to IP dosing scheduled on day 1 and will remain in clinical facility till last PK sample on day 1. Patient will be checked out on day 1 after last PK blood sample collection followed by administration of second dose of locally approved Methotrexate 2.5 mg tablet. The third dose of locally approved Methotrexate 2.5 mg tablet should be taken by patient on their own approximately 12 hours after the second dose.
The same procedure will be followed in period II.
There will be a period of at least 7 days between first dosing (IP administration) in both the study periods.
The patients will have to stay hospitalized for a period of 2 days and 1 night in each study period for their convenience and close safety monitoring.
- Conditions
- Psoriasis, Rheumatoid Arthritis
- Being tested
- Methotrexate - Amneal, Methotrexate - DAVA
- Medical subject headings
- Psoriasis, Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methotrexate - AmnealDrug
Also called Methotrexate Sodium
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
Methotrexate - DAVADrug
Also called Methotrexate Sodium
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
| Study group | Role | What they receive |
|---|---|---|
| Methotrexate - Amneal | Experimental | Methotrexate Tablets USP, 2.5 mg, single-dose in each period Receives: Drug: Methotrexate - Amneal |
| Methotrexate - DAVA | Active comparator | Methotrexate Tablets USP, 2.5 mg, single-dose in each period Receives: Drug: Methotrexate - DAVA |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Safety parameters will include monitoring of AEs, SAEs, physical examination results, vital signs and clinical laboratory results
Measured: through study completion, approximately 23 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2016 (estimated)
- Study startAug 2016
- Primary completionOct 2016 (estimated)
- Study completionOct 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PsoriasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amneal Pharmaceuticals, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Accutest Research Laboratories (I) Pvt. Ltd.
- Responsible party
- Sponsor
- Investigators
- Prayag N Shah, MD, Study director, Amneal Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02940561
- Sponsor's protocol ID
- 15-VIN-515
- Status last verified
- Oct 2016
- First submitted
- 15 Sep 2016
- Last updated
- 21 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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.
- ClinicalTrials.gov ID
- NCT02940561
- Acronym / sponsor ID
- 15-VIN-515
- Conditions
- Psoriasis, Rheumatoid Arthritis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Amneal Pharmaceuticals, LLCIndustry (pharma, biotech, devices)
- Collaborators
- Accutest Research Laboratories (I) Pvt. Ltd.
- Study start
- Aug 2016
- Primary completion
- Oct 2016 (estimated)
- Study completion
- Oct 2016 (estimated)
- First posted
- 21 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Patients will continue their own established dose of 2.5 mg tablet at 12 hours intervals for 3 doses given as a course once weekly. This dosing regimen will be kept constant throughout the study period.
On day 0 of each period, the patient will be hospitalized/ housed in the clinical facility/hospital, so patient will be administered IP dose on day 1 under supervision of trained study staff.
In supervised dosing, patient will be administered oral dose of Methotrexate Tablet 2.5 mg (Test or Reference product as per randomization schedule) with approximately 240 mL of water at ambient temperature in sitting position. Mouth check will be done by investigator/ designee followed by IP administration to verify dosing compliance.
The patient will be advised to take two subsequent doses of the locally approved drug at every 12 hours of interval after the administration of study drug on day 1.
Compliance to subsequent two doses of locally approved Methotrexate tablets 2.5 mg will be ensured as below in each period.
The dose which is to be given 12 hours after IP administration (Second dose) will be administered inside clinical facility after collection of 12 hours post-dose PK sample under supervision of trained study personnel. The next dose (third dose) will be provided to the patients with the instruction to take the same on their own. Telephonic follow-up will be made on the next day for this third dose. The same will be documented in the patient dosing log.
In period I, patient will be housed on day 0 at least 12 hours prior to IP dosing scheduled on day 1 and will remain in clinical facility till last PK sample on day 1. Patient will be checked out on day 1 after last PK blood sample collection followed by administration of second dose of locally approved Methotrexate 2.5 mg tablet. The third dose of locally approved Methotrexate 2.5 mg tablet should be taken by patient on their own approximately 12 hours after the second dose.
The same procedure will be followed in period II.
There will be a period of at least 7 days between first dosing (IP administration) in both the study periods.
The patients will have to stay hospitalized for a period of 2 days and 1 night in each study period for their convenience and close safety monitoring.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methotrexate - Amneal | Experimental | Drug: Methotrexate - AmnealMethotrexate Tablets USP, 2.5 mg, single-dose in each period |
| Methotrexate - DAVA | Active comparator | Drug: Methotrexate - DAVAMethotrexate Tablets USP, 2.5 mg, single-dose in each period |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methotrexate - AmnealAlso: Methotrexate SodiumMethotrexate 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 | Drug | Methotrexate - Amneal |
| Methotrexate - DAVAAlso: Methotrexate SodiumMethotrexate 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 | Drug | Methotrexate - DAVA |
Primary outcome
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
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.
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
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.
1 secondary outcome
Safety Parameters
Time frame: through study completion, approximately 23 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2016.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Prayag N Shah, MD study director
Amneal Pharmaceuticals
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Methotrexate - Amneal and Methotrexate - DAVA in people with Psoriasis and Rheumatoid Arthritis, run by Amneal Pharmaceuticals, LLC at 3 sites in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Prayag N Shah, MD (+91 8128671400, Dr.Prayag@amneal.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2016.