A Study in Healthy Adults and Adult Subjects With Rheumatoid Arthritis to Evaluate the Safety, Tolerability and Pharmacokinetics After Multiple Doses of ABT-494

Study Overview
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Brief Summary
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This is a phase 1, randomized, double-blind, placebo-controlled, multiple ascending dose study in healthy volunteers, multiple dose study in patients with rheumatoid arthritis and multiple dose study in healthy volunteers.

Detailed Description
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To assess the safety, tolerability and pharmacokinetics of ABT-494 in healthy volunteers and in patients with rheumatoid arthritis.

Official Title
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A Study in Healthy Adult Volunteers and Adult Subjects With Rheumatoid Arthritis to Evaluate the Safety, Tolerability, and Pharmacokinetics After Multiple Dosing of ABT-494

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: ABT-494
* Drug: Placebo
* Drug: Tofacitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Volunteers: Male and female subjects 18 to 55 years of age, inclusive. Subject is judged to be in good general health. Rheumatoid Arthritis Patients: Male and female patients 18 to 75 years of age, inclusive. Subject has a diagnosis of rheumatoid arthritis for at least six months. Subject has been on methotrexate therapy for at least three months and on a stable dose for at least four weeks. Exclusion Criteria: History or evidence of active or latent tuberculosis. History or significant allergic reaction to any drug. Use of known strong CYP3A and CYP2D6 inhibitors and CYP3A inducers within 21 days or within 5 half-lives of the respective medication, whichever is longer. Current or expected need for oral intake of at least 10 mg prednisone per day or equivalent corticosteroid therapy. History of acute inflammatory joint disease of different origin other than rheumatoid arthritis (rheumatoid arthritis patients).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Volunteers (ABT-494)<br>Multiple dosing of ABT-494 in healthy volunteers | Drug: ABT-494<br>* Oral administration of ABT-494 capsules<br>|
| Experimental: Rheumatoid Arthritis Patients<br>Multiple dosing of ABT-494 in patients with rheumatoid arthritis | Drug: ABT-494<br>* Oral administration of ABT-494 capsules<br>|
| Placebo Comparator: No treatment<br>Placebo administration in healthy volunteers and patients with rheumatoid arthritis | Drug: Placebo<br>* Oral administration of placebo capsules<br>|
| Other: Healthy Volunteers (tofa)<br>Multiple dosing of tofacitinib in healthy volunteers | Drug: Tofacitinib<br>* Oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and percentage of participants with Adverse Events |  | From first dose up to 28 days after the last dose of study drug | 
| Vital Signs | Blood pressure, pulse rate and body temperature | From first dose up to 28 days after the last dose of study drug | 
| Clinical Lab testing | Hematology, Chemistry, and Urinalysis | From date of first dose up to 28 days after the last dose of study drug | 
| Electrocardiogram (ECG) | ECGs done in triplicate; heart rate, PR interval, QT/QTc interval and QRS duration | Prior to first dose, during first dose interval, prior to last dose and until 24 hours post last dose | 
| Pharmacokinetics of ABT-494 | Cmax, Tmax, AUC, elimination rate constant and half-life | Prior to first dose up to 72 hours after the last dose of ABT-494 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of Methotrexate | Cmax, Tmax, AUC, elimination rate constant and half-life | Prior to first dose up to 48 hours after the last dose of methotrexate | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, Methotrexate, Tolerability, Pharmacokinetics, Safety, Tofacitinib