A Study to Evaluate the Pharmacokinetics of ASP1707 and Methotrexate in Patients With Rheumatoid Arthritis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02867306
• Date of registration: 11/08/2016
• Prospective Registration: No
• Primary sponsor: Astellas Pharma Global Development, Inc.
• Public title: A Study to Evaluate the Pharmacokinetics of ASP1707 and Methotrexate in Patients With Rheumatoid Arthritis
• Scientific title: A Phase 1 Open-label, Single-sequence, Drug Interaction Study to Evaluate the Pharmacokinetics of ASP1707 and Methotrexate in Patients With Rheumatoid Arthritis
• Date of first enrolment: July 25, 2016
• Target sample size: 10
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02867306
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Moldova, Republic of

Contacts

• Name: Senior Medical Director
• Affiliation: Astellas Pharma Global Development, Inc. (APGD)

Key inclusion & exclusion criteria

Inclusion Criteria:

- Female patient must either:

- Be of nonchildbearing potential: postmenopausal (defined as at least 2 years
after last regular menstrual cycle) prior to screening and follicle-stimulating
hormone (FSH) = 30 IU/mL, or

- documented surgically sterile

- Or, if of childbearing potential,

- Agree not to try to become pregnant during the study and for 28 days or 5
half-lives, whichever is longer, after the final study drug administration;

- and have a negative urine pregnancy test at screening;

- and, if heterosexually active, agree to consistently use 2 forms of highly
effective birth control (at least one of which must be a barrier method) starting
at screening and throughout the study period and for 28 days or 5 half-lives,
whichever is longer, after the final study drug administration.

- Male patient and his female spouse/partner who is of childbearing potential must be
using highly effective forms of contraception consisting of 2 forms of birth control
(1 of which must be a barrier method) starting at screening and continue throughout
the study period and for 60 days after the final study drug administration.

- Female patient must agree not to breastfeed starting at screening and throughout the
study period, and for 28 days or 5 half-lives, whichever is longer, after the final
study drug administration.

- Female patient must not donate ova starting at screening and throughout the study
period, and for 28 days or 5 half-lives, whichever is longer, after the final study
drug administration.

- Male patient must not donate sperm starting at screening and throughout the study
period, and for 60 days after the final study drug administration.

- Patient agrees not to participate in another interventional study while on treatment.

- Patient has a body mass index (BMI) of = 35 kg/m2, inclusive, and must weigh at least
50 kg at screening.

- Patient must have a clinical diagnosis of RA according to the 2010 criteria of the
American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) at
least 6 months prior to screening.

- Patient meets the ACR 1991 revised criteria for RA Global Functional Status I or II.

- Patient must be on concomitant MTX at a stable 10 to 25 mg/week dose for = 28 days
prior to day 1 and throughout the study.

- Patient on other medications (excluding MTX) for the treatment or RA at the time of
screening must be able to discontinue these medications 28 days or 5 half-lives
(whichever is longer) before first study drug dose:

o Hydroxychloroquine, cyclosporine, leflunomide and sulfasalazine

- Patient use of nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, folic
acid, low dose opioids, hormone replacement therapy (HRT), corticosteroids (prednisone
equivalent of = 5 mg/day) for treatment of RA may be allowed in the study. These
medications must be stable for = 28 days prior to screening and patients should remain
on their regimen throughout the study. Occasional acetaminophen use (less than 2
g/day) may be allowed.

- Patient use of conventional and biologic disease-modifying antirheumatic drugs
(DMARDs) used to treat RA may be allowed in this study. These medications must be
stable for 4 weeks prior to the study and remain stable during the study. Prior
approval for its use must be obtained from the sponsor.

Exclusion Criteria:

- Patient has a previous history of clinically significant systemic disease which might
confound the results of the study or pose an additional risk in administering study
drug(s) to the patient. This may include, but not be limited to, a history of drug or
food allergies, uncompensated heart failure, uncontrolled diabetes mellitus, severe
hepatic failure, severe pulmonary disease, or history of mental disease.

- Patient has a history of any malignancy in the past 5 years, except for
adequately-treated nonmelanoma skin cancer and adequately-treated-in-situ cervical
cancer.

- Patient has a positive serology test for hepatitis B surface antigen (HbsAg) or
hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) 1+2 antibodies.

- Patient received any breast cancer resistance protein (BCRP) transporter inhibitors or
substrates, with the exception of MTX, within 28 days or 5 half-lives, whichever is
longer, prior to day 1.

- Patient with liver enzyme test abnormalities, aspartate aminotransferase (AST),
alanine aminotransferase (ALT) or total bilirubin > 2 times the upper limit of normal
(ULN).

- Patient has a recent history (within the last 6 months) of drug or alcohol abuse (as
defined by the Investigator) or a positive urine screen for alcohol or drugs of
abuse/illegal drugs at screening or check-in.

- Patient has participated in a previous clinical study with treatment with ASP1707.

- Patient has received any investigational agent within 28 days or 5 half-lives,
whichever is longer, prior to day 1.

- Patient has had any significant blood loss, donated 1 unit (450 mL) of blood, or more,
or received a transfusion of any blood or blood products within 60 days or donated
plasma within 7 days prior to day 1.

- Patient is an employee of the Astellas group or vendors involved with the study.



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

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: methotrexate (MTX)

Drug: ASP1707

Primary Outcome(s)

Pharmacokinetics of methotrexate (MTX) in plasma: Cmax [Time Frame: Up to Day 8]

Pharmacokinetics of methotrexate (MTX) in plasma: AUCinf [Time Frame: Up to Day 8]

Secondary Outcome(s)

Pharmacokinetics of 7-hydroxymethotrexate (7-OH-MTX) in urine: Aelast% [Time Frame: Up to Day 8]

Pharmacokinetics of AS1948006 in plasma: tmax [Time Frame: Up to Day 8]

Pharmacokinetics of methotrexate (MTX) in plasma: CL/F [Time Frame: Up to Day 8]

Pharmacokinetics of methotrexate (MTX) in urine: Aelast [Time Frame: Up to Day 8]

Safety assessed by Laboratory Test: hematology [Time Frame: Up to Day 13]

Safety assessed by Laboratory Test: serology [Time Frame: Up to Day 13]

Pharmacokinetics of 7-hydroxymethotrexate (7-OH-MTX) in plasma: tmax [Time Frame: Up to Day 8]

Pharmacokinetics of ASP1707 in plasma: AUCtau [Time Frame: Up to Day 8]

Pharmacokinetics of ASP1707 in plasma: CL/F [Time Frame: Up to Day 8]

Pharmacokinetics of methotrexate (MTX) in plasma: AUClast [Time Frame: Up to Day 8]

Pharmacokinetics of 7-hydroxymethotrexate (7-OH-MTX) in urine: Aelast [Time Frame: Up to Day 8]

Pharmacokinetics of ASP1707 in plasma: tmax [Time Frame: Up to Day 8]

Pharmacokinetics of methotrexate (MTX) in urine: CLR [Time Frame: Up to Day 8]

Safety assessed by Laboratory Test: urinalysis [Time Frame: Up to Day 13]

Pharmacokinetics of AS1948006 in plasma: MPR [Time Frame: Up to Day 8]

Pharmacokinetics of ASP1707 in plasma: MPR [Time Frame: Up to Day 8]

Safety assessed by 12- lead electrocardiogram (ECG) [Time Frame: Up to Day 10]

Pharmacokinetics of 7-hydroxymethotrexate (7-OH-MTX) in plasma: MPR [Time Frame: Up to Day 8]

Pharmacokinetics of AS1948006 in plasma: Ctrough [Time Frame: Up to Day 8]

Pharmacokinetics of ASP1707 in plasma: Ctrough [Time Frame: Up to Day 9]

Pharmacokinetics of methotrexate (MTX) in plasma: tmax [Time Frame: Up to Day 8]

Pharmacokinetics of methotrexate (MTX) in plasma: Vz/F [Time Frame: Up to Day 8]

Safety as assessed by Adverse Events (AEs) [Time Frame: Up to Day 13]

Pharmacokinetics of AS1948006 in plasma: AUCtau [Time Frame: Up to Day 8]

Pharmacokinetics of methotrexate (MTX) in plasma: t 1/2 [Time Frame: Up to Day 8]

Number of participants with Physical Examination abnormalities and/or adverse events [Time Frame: Up to Day 10]

Pharmacokinetics of 7-hydroxymethotrexate (7-OH-MTX) in plasma: AUClast [Time Frame: Up to Day 8]

Pharmacokinetics of 7-hydroxymethotrexate (7-OH-MTX) in plasma: t 1/2 [Time Frame: Up to Day 8]

Pharmacokinetics of 7-hydroxymethotrexate (7-OH-MTX) in urine: CLR [Time Frame: Up to Day 8]

Pharmacokinetics of AS1948006 in plasma: Cmax [Time Frame: Up to Day 8]

Pharmacokinetics of ASP1707 in plasma: Cmax [Time Frame: Up to Day 8]

Safety assessed by Laboratory Test: biochemistry [Time Frame: Up to Day 13]

Pharmacokinetics of methotrexate (MTX) in urine: Aelast% [Time Frame: Up to Day 8]

Secondary ID(s)

1707-CL-3002

2016-001192-76

Source(s) of Monetary Support

Please refer to primary and secondary sponsors