Trial Outcomes & Findings for A Phase II Trial Comparing Z-102 With Placebo In Patients With Moderate To Severe Rheumatoid Arthritis (NCT NCT01369745)

Last Updated: 2014-05-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

294 participants

Primary outcome timeframe

baseline to week 12

Results posted on

2014-05-15

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Prednisolone Prednisolone 2.7 mg once daily	Dipyridamole dipyridamole 360 mg once daily	Prednisone Prednisone 5 mg once daily	Z102 2.7 mg prednisolone plus 360 mg dipyridamole once daily	Placebo placebo once daily
Overall Study STARTED	32	41	18	84	83
Overall Study COMPLETED	25	28	16	64	65
Overall Study NOT COMPLETED	7	13	2	20	18

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Prednisolone n=32 Participants 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 n=41 Participants 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 n=18 Participants 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.	Z102 n=84 Participants 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 n=83 Participants placebo once daily	Total n=258 Participants Total of all reporting groups
Age, Continuous	55.2 years STANDARD_DEVIATION 12.69 • n=5 Participants	55.9 years STANDARD_DEVIATION 9.35 • n=7 Participants	55.5 years STANDARD_DEVIATION 9.82 • n=5 Participants	54.5 years STANDARD_DEVIATION 11.53 • n=4 Participants	53.7 years STANDARD_DEVIATION 12.44 • n=21 Participants	54.6 years STANDARD_DEVIATION 11.5 • n=10 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	36 Participants n=7 Participants	17 Participants n=5 Participants	72 Participants n=4 Participants	75 Participants n=21 Participants	226 Participants n=10 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	12 Participants n=4 Participants	8 Participants n=21 Participants	32 Participants n=10 Participants

PRIMARY outcome

Timeframe: baseline to week 12

Population: 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

Outcome measures

Outcome measures
Measure	Prednisolone n=32 Participants Prednisolone 2.7 mg once daily	Dipyridamole n=39 Participants dipyridamole 360 mg once daily	Prednisone n=18 Participants Prednisone 5 mg once daily	Z102 n=82 Participants prednisolone 2.7 mg plus dipyridamole 360 mg once daily	Placebo n=81 Participants placebo once daily
Change From Baseline in DAS28-CRP at 12 Weeks	-1.147 units on a scale Standard Deviation 0.235	-0.813 units on a scale Standard Deviation 0.216	-1.237 units on a scale Standard Deviation 0.296	-0.907 units on a scale Standard Deviation 0.149	-0.538 units on a scale Standard Deviation 0.153

SECONDARY outcome

Timeframe: Baseline to week 12

Population: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 12

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: week 12

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 weeks

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.

Outcome measures

Outcome data not reported

Adverse Events

Prednisolone

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Dipyridamole

Serious events: 2 serious events

Other events: 30 other events

Deaths: 0 deaths

Prednisone

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Z102

Serious events: 5 serious events

Other events: 38 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Prednisolone n=32 participants at risk Prednisolone 2.7 mg daily	Dipyridamole n=41 participants at risk dipyridamole 360 mg once daily	Prednisone n=18 participants at risk Prednisone 5 mg once daily	Z102 n=84 participants at risk prednisolone 2.7 mg plus dipyridamole 360 mg once daily	Placebo n=83 participants at risk placebo once daily
Injury, poisoning and procedural complications Humerus Fracture	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	1.2% 1/84 • Number of events 1 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Musculoskeletal and connective tissue disorders Rheumatoid Arthritis	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	1.2% 1/84 • Number of events 1 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Nervous system disorders Sciatica	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	2.4% 2/84 • Number of events 2 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	1.2% 1/83 • Number of events 1 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Injury, poisoning and procedural complications Hip Fracture	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	1.2% 1/84 • Number of events 1 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	1.2% 1/84 • Number of events 1 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Blood and lymphatic system disorders Haemolytic Anaemia	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	1.2% 1/83 • Number of events 1 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Renal and urinary disorders Ureteric Obstruction	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	1.2% 1/83 • Number of events 1 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Vascular disorders Deep Vein Thrombosis	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	1.2% 1/83 • Number of events 1 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Cardiac disorders Angina Pectoris	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	2.4% 1/41 • Number of events 1 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
General disorders Oedema Peripheral	3.1% 1/32 • Number of events 1 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Renal and urinary disorders Calculus Ureteric	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	2.4% 1/41 • Number of events 1 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.

Other adverse events

Other adverse events
Measure	Prednisolone n=32 participants at risk Prednisolone 2.7 mg daily	Dipyridamole n=41 participants at risk dipyridamole 360 mg once daily	Prednisone n=18 participants at risk Prednisone 5 mg once daily	Z102 n=84 participants at risk prednisolone 2.7 mg plus dipyridamole 360 mg once daily	Placebo n=83 participants at risk placebo once daily
Nervous system disorders Headache	3.1% 1/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	26.8% 11/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	15.5% 13/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	4.8% 4/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Nervous system disorders Sciatica	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	2.4% 2/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	1.2% 1/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Musculoskeletal and connective tissue disorders Arthralgia	3.1% 1/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	7.3% 3/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	5.6% 1/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	6.0% 5/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	9.6% 8/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Musculoskeletal and connective tissue disorders Rheumatoid Arthritis	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	7.3% 3/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	5.6% 1/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	6.0% 5/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	4.8% 4/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Musculoskeletal and connective tissue disorders Back Pain	3.1% 1/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	7.3% 3/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	1.2% 1/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	1.2% 1/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Gastrointestinal disorders Nausea	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	4.9% 2/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	5.6% 1/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	3.6% 3/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	1.2% 1/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Gastrointestinal disorders Diarrhoea	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	2.4% 1/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	5.6% 1/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	2.4% 2/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	1.2% 1/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Gastrointestinal disorders Abdominal Upper Pain	3.1% 1/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	7.3% 3/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	1.2% 1/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	1.2% 1/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Infections and infestations Urinary Tract Infection	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	2.4% 2/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Infections and infestations Nasopharyngitis	3.1% 1/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	2.4% 1/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	5.6% 1/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	1.2% 1/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	4.8% 4/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Infections and infestations Rash Pustular	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	2.4% 2/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Infections and infestations Respiratory Tract Infection	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	2.4% 2/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Skin and subcutaneous tissue disorders Rash	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	2.4% 2/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
Ear and labyrinth disorders Vertigo	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	4.9% 2/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	1.2% 1/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
General disorders Fatigue	0.00% 0/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	2.4% 1/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	2.4% 2/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.
General disorders Oedema Peripheral	3.1% 1/32 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/41 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/18 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	0.00% 0/84 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.	2.4% 2/83 • Adverse event data were collected from the time of consent through the end of study visit at 12 weeks. 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.

Additional Information

Margaret Lee,PhD

Zalicus

Phone: 617-301-7142

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60