Rheumatoid ArthritisPhase 2SynergyNCT01369745

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

A Phase 2 study testing Prednisolone, dipyridamole and Prednisone in people with Rheumatoid Arthritis, run by Zalicus at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Thus study will test an experimental drug called Z-102 (combination of prednisolone and dipyridamole) to treat patients with moderate to severe rheumatoid arthritis. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Rheumatoid Arthritis
What is being tested?: Prednisolone, dipyridamole and Prednisone
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 294 participants
Where: 1 siteUnited States
Study dates: Jun 2011to Sep 2012
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Meet the ACR / EULAR criteria for classification of RA
Have moderate to severe RA, defined as involving a minimum (≥6 total swollen and ≥6 total tender) of the 28 joints assessed
Have screening CRP levels of at least 0.6 mg/dl and a DAS28-CRP score ≥4.5
Have been on a stable dose of conventional DMARD therapy for at least 90 days without dosage adjustment or modification and should be able to maintain the same dose of conventional DMARD therapy during study participation (with or without glucocorticoid therapy

Who cannot join

Treatment-refractory patients are excluded
Has active cardiovascular disease, unless well controlled by appropriate treatment for a minimum of 3 months prior to screening
Is taking aspirin for reasons other than for cardiovascular prophylaxis or their total daily dose is greater than 325 mg
Is currently taking steroids at a daily prednisone dose, or the equivalent, of >10 mg
Intraarticular, intramuscular, or intravenous glucocorticoids must not have been given at least 6 weeks prior to entering the study
The need to continue the use of one or multiple NSAID's at the same time, or the use of acetaminophen on a chronic basis

Show all 16Show fewer

All opiate use is prohibited
Use of any other medications or herbs used for the treatment of pain is prohibited
Patients with a history of or currently active tuberculosis as per specific country guidelines are excluded
Has uncontrolled diabetes mellitus as defined by a serum glucose >126 mg/dl
Knowingly has HIV infection or hepatitis
Has undergone administration of any investigational drug within 30 days of study initiation
All biologic agents are excluded for 90 days prior to Screening and throughout the study.
Has undergone administration of rituximab or any B-cell depleting investigational drugs within 6 months of study initiation
Has had a history of alcohol or drug abuse within the past 2 years
Has a history of hypersensitivity to glucocorticoids and/or dipyridamole

Trial locations and contacts

1 site in 1 country.

United States1 site

Zalicus Investigational Site
Toledo, Ohio, 43606

Other trials in United States

About this study

Official title: A Phase II, Double-Blind, Placebo-Controlled, Multi-Center, Randomized Withdrawal Design Trial Using Adaptive Randomization Comparing Z-102 With Placebo In Patients With Moderate To Severe Rheumatoid Arthritis

Thus study will test an experimental drug called Z-102 (combination of prednisolone and dipyridamole) to treat patients with moderate to severe rheumatoid arthritis.

Read the detailed description

The primary objective of the study was to demonstrate the efficacy of Z102 (2.7 mg prednisolone/360 mg dipyridamole) versus placebo on the Disease Activity Score 28 using C reactive protein (DAS28-CRP) in subjects with rheumatoid arthritis at the study endpoint of 12 weeks

Conditions: Rheumatoid Arthritis
Being tested: Prednisolone, dipyridamole, Prednisone, Z102, placebo
Keywords: Rheumatoid Arthritis, Moderate to severe
Medical subject headings: Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PrednisoloneDrug
Prednisolone 2.7 mg daily
dipyridamoleDrug
dipyridamole 360 mg daily
PrednisoneDrug
Prednisone 5 mg daily
Z102Drug
Also called prednisolone, dipyridamole
Prednisolone 2.7 mg plus dipyridamole 360 mg daily
placeboOther

Study groups in NCT01369745
Study group	Role	What they receive
Prednisolone	Active comparator	Prednisolone 2.7 mg daily for 12 weeks Receives: Drug: Prednisolone
dipyridamole	Active comparator	Dipyridamole 360 mg daily for 12 weeks Receives: Drug: dipyridamole
prednisone	Active comparator	Prednisone 5 mg daily for 12 weeks Receives: Drug: Prednisone
Z102 (2.7/360)	Experimental	Prednisolone 2.7 mg plus dipyridamole 360 mg daily for 12 weeks Receives: Drug: Z102
placebo	Placebo comparator	Placebo daily for 12 weeks Receives: Other: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in DAS28-CRP at 12 Weeks
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.
Measured: baseline to week 12

Secondary outcomes (4)

Change From Baseline in DAS28-CRP Individual Components at 12 Weeks
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.
Measured: Baseline to week 12
Percentage of Subjects Achieving ACR20, ACR50 and ACR70 at 12 Weeks
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.
Measured: Week 12
Multidimensional Assessment of Fatigue (MAF) at 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.
Measured: week 12
Time to Failure (Days)
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.
Measured: Baseline to 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2011Sep 2012

First posted9 Jun 2011 (estimated)
Study startJun 2011
Primary completionAug 2012
Study completionSep 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 294 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01369745
Sponsor's protocol ID: Z102-008
Acronym: Synergy
Status last verified: Apr 2014
First submitted: 7 Jun 2011
Last updated: 15 May 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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R-2487 in Patients With Sjogren's Syndrome (SjD)
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A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
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Active, not recruitingPhase 2
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All Rheumatoid Arthritis trials

Study at a glance

From the registry record, last updated by the sponsor on 15 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II, Double-Blind, Placebo-Controlled, Multi-Center, Randomized Withdrawal Design Trial Using Adaptive Randomization Comparing Z-102 With Placebo In Patients With Moderate To Severe Rheumatoid Arthritis
ClinicalTrials.gov ID: NCT01369745
Acronym / sponsor ID: Synergy / Z102-008
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis, Moderate to severe
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 294 participants (actual)
Lead sponsor: ZalicusIndustry (pharma, biotech, devices)
Study start: Jun 2011
Primary completion: Aug 2012 (actual)
Study completion: Sep 2012 (actual)
First posted: 9 Jun 2011 (estimated)
Results: Posted 30 Apr 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Thus study will test an experimental drug called Z-102 (combination of prednisolone and dipyridamole) to treat patients with moderate to severe rheumatoid arthritis.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
Prednisolone	Active comparator	Drug: PrednisolonePrednisolone 2.7 mg daily for 12 weeks
dipyridamole	Active comparator	Drug: dipyridamoleDipyridamole 360 mg daily for 12 weeks
prednisone	Active comparator	Drug: PrednisonePrednisone 5 mg daily for 12 weeks
Z102 (2.7/360)	Experimental	Drug: Z102Prednisolone 2.7 mg plus dipyridamole 360 mg daily for 12 weeks
placebo	Placebo comparator	Other: placeboPlacebo daily for 12 weeks

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Meet the ACR / EULAR criteria for classification of RA
Have moderate to severe RA, defined as involving a minimum (≥6 total swollen and ≥6 total tender) of the 28 joints assessed
Have screening CRP levels of at least 0.6 mg/dl and a DAS28-CRP score ≥4.5
Have been on a stable dose of conventional DMARD therapy for at least 90 days without dosage adjustment or modification and should be able to maintain the same dose of conventional DMARD therapy during study participation (with or without glucocorticoid therapy

Key exclusion criteria (16 listed)

Treatment-refractory patients are excluded
Has active cardiovascular disease, unless well controlled by appropriate treatment for a minimum of 3 months prior to screening
Is taking aspirin for reasons other than for cardiovascular prophylaxis or their total daily dose is greater than 325 mg
Is currently taking steroids at a daily prednisone dose, or the equivalent, of >10 mg
Intraarticular, intramuscular, or intravenous glucocorticoids must not have been given at least 6 weeks prior to entering the study

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PrednisolonePrednisolone 2.7 mg daily	Drug	Prednisolone
dipyridamoledipyridamole 360 mg daily	Drug	dipyridamole
PrednisonePrednisone 5 mg daily	Drug	prednisone
Z102Also: prednisolone, dipyridamolePrednisolone 2.7 mg plus dipyridamole 360 mg daily	Drug	Z102 (2.7/360)
placebo	Other	placebo

Primary outcome

Change From Baseline in DAS28-CRP at 12 Weeks
Time frame: baseline to week 12
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.

4 secondary outcomes

Change From Baseline in DAS28-CRP Individual Components at 12 Weeks
Time frame: Baseline to week 12
Percentage of Subjects Achieving ACR20, ACR50 and ACR70 at 12 Weeks
Time frame: Week 12
Multidimensional Assessment of Fatigue (MAF) at Week 12
Time frame: week 12
Time to Failure (Days)
Time frame: Baseline to 12 weeks

Results and safety

Results posted to the registry on 30 Apr 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Prednisolone	32	25
Dipyridamole	41	28
Prednisone	18	16
Z102	84	64
Placebo	83	65

Primary outcome: Change From Baseline in DAS28-CRP at 12 Weeks

Time frame: baseline to week 12. Mean (Standard Deviation). Unit: units on a scale

Measure	Prednisolone n = 32	Dipyridamole n = 39	Prednisone n = 18	Z102 n = 82	Placebo n = 81
Value	-1.147 (0.235)	-0.813 (0.216)	-1.237 (0.296)	-0.907 (0.149)	-0.538 (0.153)

Population analysed: 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

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data were collected from the time of consent through the end of study visit at 12 weeks.. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Prednisolone	1 of 32 (3.1%)	6 of 32 (18.8%)	Not reported
Dipyridamole	2 of 41 (4.9%)	30 of 41 (73.2%)	Not reported
Prednisone	0 of 18 (0%)	5 of 18 (27.8%)	Not reported
Z102	5 of 84 (6%)	38 of 84 (45.2%)	Not reported
Placebo	4 of 83 (4.8%)	33 of 83 (39.8%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Rheumatoid Arthritis

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Margaret Lee, PhD study director

Zalicus, Inc.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Prednisolone, dipyridamole and Prednisone in people with Rheumatoid Arthritis, run by Zalicus at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in DAS28-CRP at 12 Weeks (time frame: baseline to week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01369745.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2014.