Clinical trial NCT02867306: A Study to Evaluate the Pharmacokinetics of ASP1707 and Methotrexate in Patients With Rheumatoid Arthritis
Official title: A Phase 1 Open-label, Single-sequence, Drug Interaction Study to Evaluate the Pharmacokinetics of ASP1707 and Methotrexate in Patients With Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Keywords: methotrexate (MTX)
Pharmacokinetics
ASP1707
Rheumatoid Arthritis (RA)
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2016-08-15
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose of the study is to evaluate the effect of ASP1707 twice daily on the pharmacokinetics of once weekly oral methotrexate (MTX).

This study will also evaluate the effect of MTX on multiple-dose pharmacokinetics of ASP1707, as well as safety and tolerability of coadministration of ASP1707 and MTX in patients with rheumatoid arthritis (RA).

Detailed description: Patients will check into the clinic on Day -1 and remain in the clinic until all exit procedures have been performed on the morning of Day 10.

Eligibility 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.

Primary outcomes:
measure: Pharmacokinetics of methotrexate (MTX) in plasma: AUCinf
timeFrame: Up to Day 8
measure: Pharmacokinetics of methotrexate (MTX) in plasma: Cmax
timeFrame: Up to Day 8
Secondary outcomes:
measure: Pharmacokinetics of methotrexate (MTX) in plasma: AUClast
timeFrame: Up to Day 8
measure: Pharmacokinetics of methotrexate (MTX) in plasma: tmax
timeFrame: Up to Day 8
measure: Pharmacokinetics of methotrexate (MTX) in plasma: t 1/2
timeFrame: Up to Day 8
measure: Pharmacokinetics of methotrexate (MTX) in plasma: CL/F
timeFrame: Up to Day 8
measure: Pharmacokinetics of methotrexate (MTX) in plasma: Vz/F
timeFrame: Up to Day 8
measure: Pharmacokinetics of 7-hydroxymethotrexate (7-OH-MTX) in plasma: AUClast
timeFrame: Up to Day 8
measure: Pharmacokinetics of 7-hydroxymethotrexate (7-OH-MTX) in plasma: tmax
timeFrame: Up to Day 8
measure: Pharmacokinetics of 7-hydroxymethotrexate (7-OH-MTX) in plasma: t 1/2
timeFrame: Up to Day 8
measure: Pharmacokinetics of 7-hydroxymethotrexate (7-OH-MTX) in plasma: MPR
timeFrame: Up to Day 8
measure: Pharmacokinetics of methotrexate (MTX) in urine: Aelast
timeFrame: Up to Day 8
measure: Pharmacokinetics of methotrexate (MTX) in urine: Aelast%
timeFrame: Up to Day 8
measure: Pharmacokinetics of methotrexate (MTX) in urine: CLR
timeFrame: Up to Day 8
measure: Pharmacokinetics of 7-hydroxymethotrexate (7-OH-MTX) in urine: Aelast
timeFrame: Up to Day 8
measure: Pharmacokinetics of 7-hydroxymethotrexate (7-OH-MTX) in urine: Aelast%
timeFrame: Up to Day 8
measure: Pharmacokinetics of 7-hydroxymethotrexate (7-OH-MTX) in urine: CLR
timeFrame: Up to Day 8
measure: Pharmacokinetics of ASP1707 in plasma: AUCtau
timeFrame: Up to Day 8
measure: Pharmacokinetics of ASP1707 in plasma: Cmax
timeFrame: Up to Day 8
measure: Pharmacokinetics of ASP1707 in plasma: tmax
timeFrame: Up to Day 8
measure: Pharmacokinetics of ASP1707 in plasma: CL/F
timeFrame: Up to Day 8
measure: Pharmacokinetics of ASP1707 in plasma: Ctrough
timeFrame: Up to Day 9
measure: Pharmacokinetics of ASP1707 in plasma: MPR
timeFrame: Up to Day 8
measure: Pharmacokinetics of AS1948006 in plasma: AUCtau
timeFrame: Up to Day 8
measure: Pharmacokinetics of AS1948006 in plasma: Cmax
timeFrame: Up to Day 8
measure: Pharmacokinetics of AS1948006 in plasma: tmax
timeFrame: Up to Day 8
measure: Pharmacokinetics of AS1948006 in plasma: Ctrough
timeFrame: Up to Day 8
measure: Pharmacokinetics of AS1948006 in plasma: MPR
timeFrame: Up to Day 8
measure: Safety as assessed by Adverse Events (AEs)
timeFrame: Up to Day 13
measure: Safety assessed by Laboratory Test: hematology
timeFrame: Up to Day 13
measure: Safety assessed by Laboratory Test: biochemistry
timeFrame: Up to Day 13
measure: Safety assessed by Laboratory Test: serology
timeFrame: Up to Day 13
measure: Safety assessed by Laboratory Test: urinalysis
timeFrame: Up to Day 13
measure: Safety assessed by 12- lead electrocardiogram (ECG)
timeFrame: Up to Day 10
measure: Number of participants with Physical Examination abnormalities and/or adverse events
timeFrame: Up to Day 10
Other outcomes:
Locations:
city: Chisinau
country: Moldova, Republic of
facility: Site MD37301
Study officials:
affiliation: Astellas Pharma Global Development, Inc. (APGD)
name: Senior Medical Director
role: STUDY_DIRECTOR
References: