Trial Outcomes & Findings for Study to Assess the Safety and Efficacy of Modified-Release Prednisone (Lodotra®) Therapy in Patients With Active Rheumatoid Arthritis (NCT NCT00650078)

NCT ID: NCT00650078

Last Updated: 2024-12-18

Results Overview

Responders were defined as patients whose improvement from baseline to Visit 4 (Week 12) fulfilled all 3 of the following criteria: * \> 20% reduction in the tender joint count (0-28) * \> 20% reduction in the swollen joint count (0-28) * \> 20% reduction in 3 out of the 5 following additional measures: * Patient's assessment of pain * Patient's global assessment of disease activity * Physician's global assessment of disease activity * Functional Disability Index of the Health Assessment Questionnaire * C-reactive protein or erythrocyte sedimentation rate

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 350 participants
• Primary outcome timeframe: Week 12
• Results posted on: 2024-12-18

Participant Flow

Approximately 350 patients were to be enrolled (at screening, Visit 0), with a minimum of 6 and a maximum of 28 patients at each center. It was planned to randomize (at Visit 1) a total of 294 patients in 50-55 centers in North America and Europe (Germany, Hungary, Poland and UK). First patient enrolled March, 2008; last patient contact May, 2009.

The study consisted of a 1 week screening phase followed by a 12 week double blind treatment phase. In addition to their standard RA medication, patients received placebo during the 1 week screening phase. The purpose of the screening phase was to establish the patient's compliance with study medication and completion of diary entries.

Participant milestones

Measure	NP01 Modified Release (MR) prednisone 5 mg	Placebo
Overall Study STARTED	231	119
Overall Study COMPLETED	217	106
Overall Study NOT COMPLETED	14	13

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Assess the Safety and Efficacy of Modified-Release Prednisone (Lodotra®) Therapy in Patients With Active Rheumatoid Arthritis

Baseline characteristics by cohort

Measure	NP01 n=231 Participants Modified Release (MR) prednisone 5 mg	Placebo n=119 Participants	Total n=350 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	186 Participants n=5 Participants	95 Participants n=7 Participants	281 Participants n=5 Participants
Age, Categorical >=65 years	45 Participants n=5 Participants	24 Participants n=7 Participants	69 Participants n=5 Participants
Age, Continuous	57.1 years STANDARD_DEVIATION 9.89 • n=5 Participants	57.5 years STANDARD_DEVIATION 9.55 • n=7 Participants	57.2 years STANDARD_DEVIATION 9.76 • n=5 Participants
Sex: Female, Male Female	192 Participants n=5 Participants	102 Participants n=7 Participants	294 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	17 Participants n=7 Participants	56 Participants n=5 Participants
Region of Enrollment United States	48 participants n=5 Participants	27 participants n=7 Participants	75 participants n=5 Participants
Region of Enrollment Hungary	67 participants n=5 Participants	35 participants n=7 Participants	102 participants n=5 Participants
Region of Enrollment Canada	8 participants n=5 Participants	5 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment Poland	98 participants n=5 Participants	47 participants n=7 Participants	145 participants n=5 Participants
Region of Enrollment Germany	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment United Kingdom	9 participants n=5 Participants	3 participants n=7 Participants	12 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 12

Population: Modified Intention to Treat (mITT) efficacy population included all patients who were randomized and received at least 1 dose of study medication. Patients were analyzed according to the treatment to which they were intended to be randomized. All missing values were imputed as non-responders.

Responders were defined as patients whose improvement from baseline to Visit 4 (Week 12) fulfilled all 3 of the following criteria:

• > 20% reduction in the tender joint count (0-28)
• > 20% reduction in the swollen joint count (0-28)
• > 20% reduction in 3 out of the 5 following additional measures:

• Patient's assessment of pain
• Patient's global assessment of disease activity
• Physician's global assessment of disease activity
• Functional Disability Index of the Health Assessment Questionnaire
• C-reactive protein or erythrocyte sedimentation rate

Outcome measures

Measure	NP01 n=231 Participants Modified Release (MR) prednisone 5 mg	Placebo n=119 Participants
ACR 20 Response Rate at Visit 4	108 participants	34 participants

SECONDARY outcome

Timeframe: Week 12

Population: Modified Intention to Treat (mITT) efficacy population included all patients who were randomized and received at least 1 dose of study medication. Patients were analyzed according to the treatment to which they were intended to be randomized. Excludes those participants with missing data. Analysis used last observation carried forward imputation.

Data for the duration of morning stiffness were obtained from patient diaries. Duration of morning stiffness was the difference between the time of resolution of morning stiffness and the time of wake-up. Duration of morning stiffness is the average of the morning stiffness duration (minutes) over the last 7 days prior to visit day (including day of visit). If more than 4 assessments were missing, then the duration was set to missing. Baseline was the value recorded at Week -1 (Visit 0).

Outcome measures

Measure	NP01 n=216 Participants Modified Release (MR) prednisone 5 mg	Placebo n=107 Participants
Relative Reduction of Morning Stiffness	-55.22 Relative Change from Baseline (%) 95% Confidence Interval 63.583 • Interval -69.7 to -47.9	-34.62 Relative Change from Baseline (%) 95% Confidence Interval 67.018 • Interval -43.0 to -19.3

Adverse Events

NP01

Serious events: 1 serious events

Other events: 69 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Measure	NP01 n=231 participants at risk Modified Release (MR) prednisone 5 mg	Placebo n=119 participants at risk
Cardiac disorders myocardial ischaemia	0.00% 0/231 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later	0.84% 1/119 • Number of events 1 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later
General disorders chest discomfort	0.43% 1/231 • Number of events 1 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later	0.00% 0/119 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later
Cardiac disorders palpitations	0.43% 1/231 • Number of events 1 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later	0.00% 0/119 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later
Investigations cytology abnormal	0.00% 0/231 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later	0.84% 1/119 • Number of events 1 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later

Other adverse events

Measure	NP01 n=231 participants at risk Modified Release (MR) prednisone 5 mg	Placebo n=119 participants at risk
Musculoskeletal and connective tissue disorders arthralgia	10.4% 24/231 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later	20.2% 24/119 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later
Musculoskeletal and connective tissue disorders rheumatoid arthritis	6.5% 15/231 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later	9.2% 11/119 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later
Infections and infestations nasopharyngitis	4.8% 11/231 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later	3.4% 4/119 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later
Nervous system disorders headache	3.9% 9/231 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later	4.2% 5/119 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later
Infections and infestations bronchitis	1.3% 3/231 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later	4.2% 5/119 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later
Vascular disorders hypertension	2.2% 5/231 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later	0.84% 1/119 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later
Skin and subcutaneous tissue disorders rash	1.7% 4/231 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later	0.84% 1/119 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later
Gastrointestinal disorders diarrhea	1.7% 4/231 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later	0.84% 1/119 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later
Musculoskeletal and connective tissue disorders back pain	1.3% 3/231 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later	0.84% 1/119 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later
Renal and urinary disorders hematuria	0.43% 1/231 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later	2.5% 3/119 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later
Gastrointestinal disorders vomiting	1.3% 3/231 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later	0.84% 1/119 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later
General disorders oedema peripheral	0.87% 2/231 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later	1.7% 2/119 • Initiation of double blind treatment until end of treatment or 30 days after last study drug administration, whicever occurred later

Additional Information

Senior Vice President, Clinical Development & Operations

Horizon Pharma

Phone: 224-383-3012

Email: agrahn@horizonpharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee The first publication shall be the presentation of a joint, multicenter publication of the Study results. If such a multicenter publication is not submitted within 24 months after conclusion of the Study at all sites, INSTITUTION/INVESTIGATOR may publish the results from the INSTITUTION'S site individually, provided that it is submitted to SPONSOR for review and comment 60 days prior to submission for publication.
• Publication restrictions are in place

Restriction type: OTHER