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Trial record 31 of 117 for:    "Connective Tissue Disease" | "Methylprednisolone"

A Phase II Trial Comparing Z-102 With Placebo In Patients With Moderate To Severe Rheumatoid Arthritis (Synergy)

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ClinicalTrials.gov Identifier: NCT01369745
Recruitment Status : Completed
First Posted : June 9, 2011
Results First Posted : April 30, 2014
Last Update Posted : May 15, 2014
Sponsor:
Information provided by (Responsible Party):
Zalicus

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: Prednisolone
Drug: dipyridamole
Drug: Prednisone
Drug: Z102
Other: placebo
Enrollment 294
Recruitment Details  
Pre-assignment Details A total of 294 subjects entered the titration phase. Of these, 258 subjects completed the titration phase, were randomized to treatment, received at least one dose of study drug and constitute the safety population. Of these, 252 subjects provided at least one post-baseline measurement of the primary endpoint and constitute the efficacy population.
Arm/Group Title Prednisolone Dipyridamole Prednisone Z102 Placebo
Hide Arm/Group Description Prednisolone 2.7 mg once daily dipyridamole 360 mg once daily Prednisone 5 mg once daily 2.7 mg prednisolone plus 360 mg dipyridamole once daily placebo once daily
Period Title: Overall Study
Started 32 41 18 84 83
Completed 25 28 16 64 65
Not Completed 7 13 2 20 18
Arm/Group Title Prednisolone Dipyridamole Prednisone Z102 Placebo Total
Hide Arm/Group Description Prednisolone 2.7 mg once daily The trial would progress from Stage 1 to Stage 2 if the posterior probability that Z102 is superior to placebo was greater than 0.975. dipyridamole 360 mg once daily The trial would progress from Stage 2 to Stage 3 if the posterior probability that Z102 is superior to dipyridamole was greater than 0.975. Prednisone 5 mg once daily The trial would progress from Stage 2 to Stage 4 if the posterior probability that Z102 is superior to prednisolone 2.7 was greater than 0.975. prednisolone 2.7 mg plus dipyridamole 360 mg once daily The trial would progress from Stage 3 to Stage 5 if the posterior probability that Z102 is superior to prednisolone 2.7 was greater than 0.975. placebo once daily Total of all reporting groups
Overall Number of Baseline Participants 32 41 18 84 83 258
Hide Baseline Analysis Population Description
population randomized to double blind phase of study and recieved at least one dose of study drug
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 32 participants 41 participants 18 participants 84 participants 83 participants 258 participants
55.2  (12.69) 55.9  (9.35) 55.5  (9.82) 54.5  (11.53) 53.7  (12.44) 54.6  (11.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 41 participants 18 participants 84 participants 83 participants 258 participants
Female
26
  81.3%
36
  87.8%
17
  94.4%
72
  85.7%
75
  90.4%
226
  87.6%
Male
6
  18.8%
5
  12.2%
1
   5.6%
12
  14.3%
8
   9.6%
32
  12.4%
1.Primary Outcome
Title Change From Baseline in DAS28-CRP at 12 Weeks
Hide Description

The primary efficacy endpoint was the mean change in Disease Activity Score 28 using C-reactive protein (DAS28-CRP) from baseline to Week 12.

The DAS28-CRP is a composite measure of inflammation in Rheumatoid Arthritis and incorporates a tender and swollen joint count, CRP and Patient Global Assessment of Disease Activity expressed in a Gaussian distribution of variables ranging from 0 to 10. A DAS28-CRP score of <3.2 suggests a low level of disease activity, while a score of >5.1 suggests a high level of disease activity. Using the DAS-CRP as a continuous scale allows investigators (and clinicians) to measure a clinically meaningful endpoint following institution of a therapeutic intervention. In RA, clinical remission would therefore be graded as a DAS28 score of ≤3.2 with disease flare accompanying scores of ≥5.1; well-controlled disease is best characterized as fitting in between these two scores.

Time Frame baseline to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis population includes all 252 subjects who received at least one dose of study drug after randomization and who provided at least one post-baseline measurement of the primary endpoint
Arm/Group Title Prednisolone Dipyridamole Prednisone Z102 Placebo
Hide Arm/Group Description:
Prednisolone 2.7 mg once daily
dipyridamole 360 mg once daily
Prednisone 5 mg once daily
prednisolone 2.7 mg plus dipyridamole 360 mg once daily
placebo once daily
Overall Number of Participants Analyzed 32 39 18 82 81
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.147  (0.235) -0.813  (0.216) -1.237  (0.296) -0.907  (0.149) -0.538  (0.153)
2.Secondary Outcome
Title Change From Baseline in DAS28-CRP Individual Components at 12 Weeks
Hide Description

The mean change in the individual components of the Disease Activity Score 28 using C-reactive protein (DAS28-CRP) from baseline to Week 12 which included individual assessment of Tender Joint Count (28-joint assessment), Swollen Joint Count (28-joint assessment), Patient Global Assessment of Disease Activity and absolute CRP level. In each case, higher scores indicate more disease activity.

The DAS28-CRP is a composite measure of inflammation in Rheumatoid Arthritis and incorporates a tender and swollen joint count, CRP and Patient Global Assessment of Disease Activity expressed in a Gaussian distribution of variables ranging from 0 to 10. A DAS28-CRP score of <3.2 suggests a low level of disease activity, while a score of >5.1 suggests a high level of disease activity.

Time Frame Baseline to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Because the study never progressed past the first stage of the adaptive randomization, the number of subjects who were allocated to the dipyridamole 360 mg, prednisolone 2.7 mg, and prednisone 5 mg treatment arms was insufficient (underpowered) to allow analysis of the secondary objectives.
Arm/Group Title Prednisolone Dipyridamole Prednisone Z102 Placebo
Hide Arm/Group Description:
Prednisolone 2.7 mg once daily
dipyridamole 360 mg once daily
Prednisone 5 mg once daily
prednisolone 2.7 mg plus dipyridamole 360 mg once daily
placebo once daily
Overall Number of Participants Analyzed 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Percentage of Subjects Achieving ACR20, ACR50 and ACR70 at 12 Weeks
Hide Description The American College of Rheumatology (ACR) 20 is a widely accepted composite index of improvement in RA proposed by the ACR (Fransen and van Riel 2009). ACR20 refers to a composite improvement of 20% in swollen joint count, tender joint count, and 3 or more of the following 5 measures:Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, Patient Pain VAS, Patient's self-addressed disability (HAQ) (Arnet 1988 and Felson 1995), Acute-phase reactant (ESR or CRP) The ACR 50 and ACR 70 are similar tools, used to indicate 50% and 70% improvement, respectively.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Because the study never progressed past the first stage of the adaptive randomization, the number of subjects who were allocated to the dipyridamole 360 mg, prednisolone 2.7 mg, and prednisone 5 mg treatment arms was insufficient (underpowered) to allow analysis of the secondary objectives.
Arm/Group Title Prednisolone Dipyridamole Prednisone Z102 Placebo
Hide Arm/Group Description:
Prednisolone 2.7 mg once daily
dipyridamole 360 mg once daily
Prednisone 5 mg once daily
prednisolone 2.7 mg plus dipyridamole 360 mg once daily
placebo once daily
Overall Number of Participants Analyzed 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Multidimensional Assessment of Fatigue (MAF) at Week 12
Hide Description

The Multidimensional Assessment of Fatigue (MAF) scale contains 16 items and measures four dimensions of fatigue: severity (#1-2), distress (#3), degree of interference in activities of daily living (#4-14), and timing (#15-16). Fourteen items contain numerical rating scales (#1-14) and two items have multiple-choice responses (#15-16). Respondents are asked to reflect on fatigue patterns for the past week.

To calculate the Global Fatigue Index (GFI): Convert item #15 to a 0-10 scale by multiplying each score by 2.5 and then sum items #1, 2, 3, average #4-14, and newly scored item #15.

Scores range from 1 (no fatigue) to 50 (severe fatigue). Do not assign a score to items #4-14 if respondent indicated they "do not do any activity for reasons other than fatigue." If respondents select no fatigue on item #1, assign a zero to items #2-16. Item #16 is not included in the Global Fatigue Index.

Time Frame week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Because the study never progressed past the first stage of the adaptive randomization, the number of subjects who were allocated to the dipyridamole 360 mg, prednisolone 2.7 mg, and prednisone 5 mg treatment arms was insufficient (underpowered) to allow analysis of the secondary objectives.
Arm/Group Title Prednisolone Dipyridamole Prednisone Z102 Placebo
Hide Arm/Group Description:
Prednisolone 2.7 mg once daily
dipyridamole 360 mg once daily
Prednisone 5 mg once daily
prednisolone 2.7 mg plus dipyridamole 360 mg once daily
placebo once daily
Overall Number of Participants Analyzed 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Time to Failure (Days)
Hide Description Patients will be monitored for addition of any DMARD or withdrawal due to flare. The time to failure is defined as the duration of study participation (in days) until a qualifying event or completion of study treatment, whichever comes first.
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Because the study never progressed past the first stage of the adaptive randomization, the number of subjects who were allocated to the dipyridamole 360 mg, prednisolone 2.7 mg, and prednisone 5 mg treatment arms was insufficient (underpowered) to allow analysis of the secondary objectives.
Arm/Group Title Prednisolone Dipyridamole Prednisone Z102 Placebo
Hide Arm/Group Description:
Prednisolone 2.7 mg once daily
dipyridamole 360 mg once daily
Prednisone 5 mg once daily
prednisolone 2.7 mg plus dipyridamole 360 mg once daily
placebo once daily
Overall Number of Participants Analyzed 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Adverse event data were collected from the time of consent through the end of study visit at 12 weeks.
Adverse Event Reporting Description Adverse events are reported for the safety population of 258 subjects randomized to the double blind study phase and who received at least one dose of study drug.
 
Arm/Group Title Prednisolone Dipyridamole Prednisone Z102 Placebo
Hide Arm/Group Description Prednisolone 2.7 mg daily dipyridamole 360 mg once daily Prednisone 5 mg once daily prednisolone 2.7 mg plus dipyridamole 360 mg once daily placebo once daily
All-Cause Mortality
Prednisolone Dipyridamole Prednisone Z102 Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Prednisolone Dipyridamole Prednisone Z102 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/32 (3.13%)      2/41 (4.88%)      0/18 (0.00%)      5/84 (5.95%)      4/83 (4.82%)    
Blood and lymphatic system disorders           
Thrombocytopenia * 1  0/32 (0.00%)  0 0/41 (0.00%)  0 0/18 (0.00%)  0 1/84 (1.19%)  1 0/83 (0.00%)  0
Haemolytic Anaemia * 1  0/32 (0.00%)  0 0/41 (0.00%)  0 0/18 (0.00%)  0 0/84 (0.00%)  0 1/83 (1.20%)  1
Cardiac disorders           
Angina Pectoris * 1  0/32 (0.00%)  0 1/41 (2.44%)  1 0/18 (0.00%)  0 0/84 (0.00%)  0 0/83 (0.00%)  0
General disorders           
Oedema Peripheral * 1  1/32 (3.13%)  1 0/41 (0.00%)  0 0/18 (0.00%)  0 0/84 (0.00%)  0 0/83 (0.00%)  0
Injury, poisoning and procedural complications           
Hip Fracture * 1  0/32 (0.00%)  0 0/41 (0.00%)  0 0/18 (0.00%)  0 1/84 (1.19%)  1 0/83 (0.00%)  0
Humerus Fracture * 1  0/32 (0.00%)  0 0/41 (0.00%)  0 0/18 (0.00%)  0 1/84 (1.19%)  1 0/83 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Rheumatoid Arthritis * 1  0/32 (0.00%)  0 0/41 (0.00%)  0 0/18 (0.00%)  0 1/84 (1.19%)  1 0/83 (0.00%)  0
Nervous system disorders           
Sciatica * 1  0/32 (0.00%)  0 0/41 (0.00%)  0 0/18 (0.00%)  0 2/84 (2.38%)  2 1/83 (1.20%)  1
Renal and urinary disorders           
Ureteric Obstruction * 1  0/32 (0.00%)  0 0/41 (0.00%)  0 0/18 (0.00%)  0 0/84 (0.00%)  0 1/83 (1.20%)  1
Calculus Ureteric * 1  0/32 (0.00%)  0 1/41 (2.44%)  1 0/18 (0.00%)  0 0/84 (0.00%)  0 0/83 (0.00%)  0
Vascular disorders           
Deep Vein Thrombosis * 1  0/32 (0.00%)  0 0/41 (0.00%)  0 0/18 (0.00%)  0 0/84 (0.00%)  0 1/83 (1.20%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (14.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Prednisolone Dipyridamole Prednisone Z102 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/32 (18.75%)      30/41 (73.17%)      5/18 (27.78%)      38/84 (45.24%)      33/83 (39.76%)    
Ear and labyrinth disorders           
Vertigo * 1  0/32 (0.00%)  2/41 (4.88%)  0/18 (0.00%)  1/84 (1.19%)  0/83 (0.00%) 
Gastrointestinal disorders           
Nausea * 1  0/32 (0.00%)  2/41 (4.88%)  1/18 (5.56%)  3/84 (3.57%)  1/83 (1.20%) 
Diarrhoea * 1  0/32 (0.00%)  1/41 (2.44%)  1/18 (5.56%)  2/84 (2.38%)  1/83 (1.20%) 
Abdominal Upper Pain * 1  1/32 (3.13%)  3/41 (7.32%)  0/18 (0.00%)  1/84 (1.19%)  1/83 (1.20%) 
General disorders           
Fatigue * 1  0/32 (0.00%)  1/41 (2.44%)  0/18 (0.00%)  0/84 (0.00%)  2/83 (2.41%) 
Oedema Peripheral * 1  1/32 (3.13%)  0/41 (0.00%)  0/18 (0.00%)  0/84 (0.00%)  2/83 (2.41%) 
Infections and infestations           
Urinary Tract Infection * 1  0/32 (0.00%)  0/41 (0.00%)  0/18 (0.00%)  2/84 (2.38%)  0/83 (0.00%) 
Nasopharyngitis * 1  1/32 (3.13%)  1/41 (2.44%)  1/18 (5.56%)  1/84 (1.19%)  4/83 (4.82%) 
Rash Pustular * 1  0/32 (0.00%)  0/41 (0.00%)  0/18 (0.00%)  0/84 (0.00%)  2/83 (2.41%) 
Respiratory Tract Infection * 1  0/32 (0.00%)  0/41 (0.00%)  0/18 (0.00%)  0/84 (0.00%)  2/83 (2.41%) 
Musculoskeletal and connective tissue disorders           
Arthralgia * 1  1/32 (3.13%)  3/41 (7.32%)  1/18 (5.56%)  5/84 (5.95%)  8/83 (9.64%) 
Rheumatoid Arthritis * 1  0/32 (0.00%)  3/41 (7.32%)  1/18 (5.56%)  5/84 (5.95%)  4/83 (4.82%) 
Back Pain * 1  1/32 (3.13%)  3/41 (7.32%)  0/18 (0.00%)  1/84 (1.19%)  1/83 (1.20%) 
Nervous system disorders           
Headache * 1  1/32 (3.13%)  11/41 (26.83%)  0/18 (0.00%)  13/84 (15.48%)  4/83 (4.82%) 
Sciatica * 1  0/32 (0.00%)  0/41 (0.00%)  0/18 (0.00%)  2/84 (2.38%)  1/83 (1.20%) 
Skin and subcutaneous tissue disorders           
Rash * 1  0/32 (0.00%)  0/41 (0.00%)  0/18 (0.00%)  2/84 (2.38%)  0/83 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (14.0)
The study did not progress past the first stage of adaptive randomization. The number of subjects allocated to the dipyridamole 360 mg, prednisolone 2.7 mg, and prednisone 5 mg arms was insufficient to allow analysis of the secondary objectives.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Margaret Lee,PhD
Organization: Zalicus
Phone: 617-301-7142
Responsible Party: Zalicus
ClinicalTrials.gov Identifier: NCT01369745     History of Changes
Other Study ID Numbers: Z102-008
First Submitted: June 7, 2011
First Posted: June 9, 2011
Results First Submitted: February 10, 2014
Results First Posted: April 30, 2014
Last Update Posted: May 15, 2014