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

NCT01741493 | Completed Phase 1

• 1 other identifier: M13-845
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; Methotrexate; Tolerability; Pharmacokinetics; Safety; Tofacitinib

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (1)

• Pharmacokinetics of Methotrexate

  Prior to first dose up to 48 hours after the last dose of methotrexate

Study Arms (4)

Healthy Volunteers (ABT-494)

EXPERIMENTAL

Multiple dosing of ABT-494 in healthy volunteers

Drug: ABT-494

Rheumatoid Arthritis Patients

EXPERIMENTAL

Multiple dosing of ABT-494 in patients with rheumatoid arthritis

Drug: ABT-494

No treatment

PLACEBO COMPARATOR

Placebo administration in healthy volunteers and patients with rheumatoid arthritis

Drug: Placebo

Healthy Volunteers (tofa)

OTHER

Multiple dosing of tofacitinib in healthy volunteers

Drug: Tofacitinib

Interventions

ABT-494 DRUG

Oral administration of ABT-494 capsules

Healthy Volunteers (ABT-494); Rheumatoid Arthritis Patients

Placebo DRUG

Oral administration of placebo capsules

No treatment

Tofacitinib DRUG

Oral administration

Healthy Volunteers (tofa)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Study Sites (5)

Site Reference ID/Investigator# 95817

Miami, Florida, 33136, United States

Location

Site Reference ID/Investigator# 95816

Cincinnati, Ohio, 45255, United States

Location

Site Reference ID/Investigator# 95815

Duncansville, Pennsylvania, 16635, United States

Location

Site Reference ID/Investigator# 92153

Austin, Texas, 78744, United States

Location

Site Reference ID/Investigator# 97177

Orem, Utah, 84058, United States

Location

Related Publications (2)

• Mohamed MF, Camp HS, Jiang P, Padley RJ, Asatryan A, Othman AA. Pharmacokinetics, Safety and Tolerability of ABT-494, a Novel Selective JAK 1 Inhibitor, in Healthy Volunteers and Subjects with Rheumatoid Arthritis. Clin Pharmacokinet. 2016 Dec;55(12):1547-1558. doi: 10.1007/s40262-016-0419-y.

  PMID: 27272171 RESULT

• Klunder B, Mohamed MF, Othman AA. Population Pharmacokinetics of Upadacitinib in Healthy Subjects and Subjects with Rheumatoid Arthritis: Analyses of Phase I and II Clinical Trials. Clin Pharmacokinet. 2018 Aug;57(8):977-988. doi: 10.1007/s40262-017-0605-6.

  PMID: 29076110 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

upadacitinib; tofacitinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Steven Jungerwirth, MD

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2012
• First Posted: December 5, 2012
• Study Start: November 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: November 20, 2017

Record last verified: 2014-01

Locations

US (5)