A Study of the Effects of Oral Prednisone in Patients With Rheumatoid Arthritis (MK0000-088)

• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

The study will compare the effects of prednisone vs placebo on synovial blood flow and overall DAS (disease activity score) in patients with rheumatoid arthritis.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: Prednisone 15 mg; Drug: Placebo Tablets; Drug: Prednisone 7.5 mg; Drug: Placebo Over-Encapsulated Tablets	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Parallel Group, Placebo Controlled Study to Access the Effects of Oral Prednisone on Clinical Efficacy and the Power Doppler Ultrasound Signal of Synovium in Patients With Rheumatoid Arthritis
• Study Start Date: September 2008
• Actual Primary Completion Date: September 2009
• Actual Study Completion Date: September 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Prednisone 15 mg; Prednisone 15 mg tablets once daily for 15 days	Drug: Prednisone 15 mg; Prednisone 15 mg tablets once daily for 15 days.; Other Name: Prednisone
Placebo Comparator: Placebo 15 mg; Prednisone 15 mg placebo tablets once daily for 15 days	Drug: Placebo Tablets; Prednisone placebo tablets once daily for 15 days.
Experimental: Prednisone 7.5 mg; Prednisone 7.5 mg over-encapsulated tablets once daily for 15 days As per adaptive dose-ranging design, this arm was added to the study because a difference between prednisone 15 mg and placebo was demonstrated during interim analysis.	Drug: Prednisone 7.5 mg; Prednisone 7.5 mg over-encapsulated tablets once daily for 15 days; Other Name: Prednisone
Placebo Comparator: Placebo 7.5 mg; Prednisone 7.5 mg placebo over-encapsulated tablets once daily for 15 days As per adaptive dose-ranging design, this arm was added to the study because a difference between prednisone 15 mg and placebo was demonstrated during interim analysis.	Drug: Placebo Over-Encapsulated Tablets; Prednisone 7.5 mg placebo over-encapsulated tablets once daily for 15 days

Outcome Measures

Primary Outcome Measures :

1. Synovial Blood Flow [ Time Frame: Baseline and Day 14 ]
   Synovial Blood Flow was measured as the 2-dimensional quantitative Transverse Power Doppler Area summed over each of the 10 metacarpophalangeal joints (10MCP 2D Trans PDA). The PDA is a count of the number of pixels with power Doppler signal, uncorrected by pixel intensity, within an expert drawn region of interest encompassing the synovium and excluding digital vessels in a standardized 2D transverse image of the joint. A higher pixel count relates to greater synovial blood flow. A decrease in pixel count relates to a reduction in synovial blood flow.

Secondary Outcome Measures :

1. Disease Activity Score 28 (DAS28) (C-reactive Protein [CRP]) [ Time Frame: Baseline and Day 14 ]

   The DAS28(CRP) is a measure of disease activity with components which include the tender joint count (TJC) & swollen joint count (SJC) (each out of 28 joints counted), a Global Health (GH) index (100 mm visual analog scale [VAS]), and the CRP (in mg/L measured from lab test). The scoring formula was:

   DAS28(CRP) = 0.56*SQR(TJC28) + 0.28*SQR(SJC28) + 0.36*ln(CRP+1) + 0.014*GH(VAS) + 0.96.

   Where SQR is square root and ln is natural log.

   The formula produces a score from 0 to 10: >5.1 means high disease activity; <3.2 means low disease activity, <2.6 is generally considered remission.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patient is willing to limit alcohol intake to 3 or less beverages per day
• Patient agrees to use only acetaminophen/paracetamol for breakthrough pain

Exclusion Criteria:

• Patient has other inflammatory arthritis (e.g. lupus). Patient has had major surgery or donated or lost 1 unit of blood in the last 4 weeks
• Patient has a history of drug or alcohol abuse in the last 2 years
• Patient has had a vaccine (with a live or attenuated virus) in the last two weeks

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Monitor; Merck Sharp & Dohme Corp.

More Information

Publications of Results:

Seymour MW, Kelly S, Beals CR, Malice MP, Bolognese JA, Dardzinski BJ, Cheng AS, Cummings CE, Smugar SS, McClinton C, Fox A, Dooley WM, Pitzalis C, Taylor PC. Ultrasound of metacarpophalangeal joints is a sensitive and reliable endpoint for drug therapies in rheumatoid arthritis: results of a randomized, two-center placebo-controlled study. Arthritis Res Ther. 2012 Sep 12;14(5):R198. doi: 10.1186/ar4034.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT00746512 History of Changes
• Other Study ID Numbers: 0000-088; 2008_531
• First Posted: September 4, 2008
• Results First Posted: April 8, 2011
• Last Update Posted: May 29, 2015
• Last Verified: May 2015

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Prednisone; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents