Evaluation of 2 Oral Doses of PG-760564 in Rheumatoid Arthritis (RA) Patients Receiving Methotrexate

• Sponsor: Procter and Gamble (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00369928
• Collaborator: (none)
• Enrollment: 254
• Locations: 53
• Arms: 3
• Duration (Months): 17
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This will be a 12-week, double-blind, randomized, placebo-controlled, parallel group, multicenter study to evaluate the safety, efficacy, and PK of oral administration of PG-760564 in adult patients with active RA receiving treatment with MTX. Two oral doses of PG-760564 will be evaluated: 25 mg BID and 100 mg BID. The study will consist of a screening visit followed by a washout period for all disease modifying antirheumatic drugs (DMARDs) and anti-cytokine therapies except MTX. After the washout period, patients determined to be eligible will be randomized to receive either 25 mg BID or 100 mg BID of oral PG-760564, or placebo for 12 weeks. There will be 6 treatment visits and a follow-up visit 4 weeks after the last treatment visit. The primary efficacy endpoint will be the proportion of patients meeting the ACR 20 response criteria after 12 weeks of treatment.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: PG-760564; Drug: Placebo dose; Drug: PG-760564	Phase 2

Detailed Description

The study will be conducted in North America and Europe at approximately 50 to 60 sites. Approximately 270 patients will be randomized, of which 189 are expected to complete the study.

The study will consist of a screening visit followed by a washout period for all disease modifying antirheumatic drugs (DMARDs) and anti-cytokine therapies except MTX. The washout period will be 4 weeks for sulfasalazine, hydroxychloroquine, azathioprine, D-penicillamine, etanercept, and anakinra, 8 weeks for gold, infliximab, and adalimumab, and 12 weeks for abatacept.

After the washout period, the patients determined to be eligible will be randomized to receive either 25 mg BID or 100 mg BID of oral PG-760564, or placebo for 12 weeks. There will be 6 treatment visits (Weeks 1, 2, 4, 6, 8, and 12) and a follow-up visit 4 weeks after the last treatment visit (Week 16). Patients will not initiate new therapies until after the 4-week follow-up is completed. Liver function tests will be evaluated at every visit.

The primary efficacy endpoint will be the proportion of patients meeting the ACR 20 response criteria after 12 weeks of treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 254 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of 2 Oral Doses, 25 mg Twice Daily and 100 mg Twice Daily, of PG-760564 in Adult Patients With RA Receiving Methotrexate
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo, oral dose, BID	Drug: Placebo dose; placebo, BID, oral for 12 weeks
Experimental: 25 mg PG-760564 25 mg BID, of oral PG-760564	Drug: PG-760564; 25 mg BID, of oral PG-760564
Experimental: 100 mg PG-760564 100 mg BID, of oral PG-760564	Drug: PG-760564; 100 mg BID, of oral PG-760564

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients Meeting American College of Rheumatology 20 Response Criteria (ACR20) at 12weeks [12 weeks]

   percent, relative to baseline, of patients meeting the American College of Rheumatology 20 response criteria (ACR20) at 12weeks

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Meet American College of Rheumatology (ACR) criteria for Rheumatoid Arthritis

• Disease duration of at least 6 months

• Must be treated with Methotrexate for at least 24 weeks

• At least 6 swollen joints and 6 tender joints

• Washout required for other Disease Modifying Anti-rheumatic Drugs (DMARDs)

• Women of childbearing age and all males must use acceptable method of birth control

Exclusion Criteria:

• Tuberculosis

• Malignancies

• Abnormal electrocardiograms as described in the protocol

• Current infection or recurrent infections or immunodeficiency

• Liver diseases and abnormalities in liver function tests as described in the protocol

• Autoimmune diseases other than RA except Sjogren's syndrome secondary to RA;

• History of demyelization diseases

• Any condition that in the opinion of the investigator could be detrimental to patients enrolling in the study including clinically important changes in laboratory values and other diseases described in the protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Facility	Hot Springs	Arkansas	United States	71913
2	Research Facility	Beverly Hills	California	United States	90211
3	Research Facility	Mission Viejo	California	United States	92691
4	Research Facility	Chiefland	Florida	United States	32626
5	Research Facility	Dunedin	Florida	United States	34698
6	Research Facility	Ft. Lauderdale	Florida	United States	33334
7	Research Facility	Tavares	Florida	United States	32778
8	Research Facility	Decatur	Georgia	United States	30033
9	Research Facility	Marietta	Georgia	United States	30060
10	Research Facility	Rome	Georgia	United States	30165
11	Research Facility	Meridian	Idaho	United States	83642
12	Research Facility	New Orleans	Louisiana	United States	70121
13	Research Facility	Omaha	Nebraska	United States	68134
14	Research Facility	Elizabeth	New Jersey	United States	07202
15	Research Facility	Plainview	New York	United States	11803
16	Research Facility	Charlotte	North Carolina	United States	28209
17	Research Facility	Wilmington	North Carolina	United States	28401
18	Research Facility	Minot	North Dakota	United States	58701
19	Research Facility	Duncansville	Pennsylvania	United States	16635
20	Research Facility	Erie	Pennsylvania	United States	16508
21	Research Facility	Austin	Texas	United States	78705
22	Research Facility	Dallas	Texas	United States	75231
23	Research Facility	Dallas	Texas	United States	75235
24	Research Facility	San Antonio	Texas	United States	78217
25	Research Facility	Ceska Lipa		Czech Republic
26	Research Facility	Hustopece		Czech Republic
27	Research Facility	Prague		Czech Republic
28	Research Facility	Uherske Hradiste		Czech Republic
29	Research Facility	Zlin		Czech Republic
30	Research Facility	Balatonfüred		Hungary
31	Research Facility	Budapest		Hungary
32	Research Facility	Eger		Hungary
33	Research Facility	Gyor		Hungary
34	Research Facility	Gyula		Hungary
35	Research Facility	Szolnok		Hungary
36	Research Facility	Den Haag		Netherlands	2545 CH
37	Research Facility	Częstochowa		Poland	42-200
38	Research Facility	Działdowo		Poland	13-200
39	Research Facility	Elbląg		Poland	83-300
40	Research Facility	Konskie		Poland	26-200
41	Research Facility	Krakow		Poland	30-510
42	Research Facility	Krakow		Poland	31-121
43	Research Facility	Lodz		Poland	33-513
44	Research Facility	Lublin		Poland	20-954
45	Research Facility	Poznań		Poland	60-733
46	Research Facility	Sopot		Poland	81-759
47	Research Facility	Szczecin		Poland	71-252
48	Research Facility	Torun		Poland	85-168
49	Research Facility	Warszawa		Poland	00-909
50	Research Facility	Ashford		United Kingdom	TW15 3AA
51	Research Facility	Cambridge		United Kingdom
52	Research Facility	Glasgow		United Kingdom	G20 0XA
53	Research Facility	Liverpool		United Kingdom	L9 7AL

Sponsors and Collaborators

• Procter and Gamble

Investigators

• Study Director: Muhammad Rehman, MD, Procter and Gamble

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00369928
• Other Study ID Numbers: 2006012
• First Posted: Aug 30, 2006
• Last Update Posted: Sep 8, 2011
• Last Verified: Aug 1, 2011

• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

Participant Flow

Arm/Group Title	Placebo	25 mg PG-760564 BID	100 mg PG-760564 BID
Arm/Group Description	Placebo, oral dose, BID	25 mg BID, of oral PG-760564	100 mg BID, of oral PG-760564
Period Title: Overall Study
STARTED	85	85	86
COMPLETED	77	69	66
NOT COMPLETED	8	16	20

Baseline Characteristics

Arm/Group Title	Placebo	25 mg PG-760564 BID	100 mg PG-760564 BID	Total
Arm/Group Description	Placebo, oral dose, BID	25 mg BID, of oral PG-760564	100 mg BID, of oral PG-760564	Total of all reporting groups
Overall Participants	85	85	86	256
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	75 88.2%	78 91.8%	79 91.9%	232 90.6%
>=65 years	10 11.8%	7 8.2%	7 8.1%	24 9.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.52 (11.04)	50.39 (11.68)	54.70 (9.31)	52.21 (10.83)
Sex: Female, Male (Count of Participants)
Female	64 75.3%	65 76.5%	66 76.7%	195 76.2%
Male	21 24.7%	20 23.5%	20 23.3%	61 23.8%
Region of Enrollment (participants) [Number]
United States	9 10.6%	11 12.9%	9 10.5%	29 11.3%
Poland	45 52.9%	42 49.4%	49 57%	136 53.1%
United Kingdom	3 3.5%	0 0%	0 0%	3 1.2%
Czech Republic	18 21.2%	23 27.1%	16 18.6%	57 22.3%
Hungary	10 11.8%	9 10.6%	12 14%	31 12.1%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Meeting American College of Rheumatology 20 Response Criteria (ACR20) at 12weeks
Description	percent, relative to baseline, of patients meeting the American College of Rheumatology 20 response criteria (ACR20) at 12weeks
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	25 mg PG-760564 BID	100 mg PG-760564 BID
Arm/Group Description	Placebo, oral dose, BID	25 mg BID, of oral PG-760564	100 mg BID, of oral PG-760564
Measure Participants	85	85	86
Number (95% Confidence Interval) [percent meeting ACR 20]	60	56	54

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 25 mg PG-760564 BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.982
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 80%; 0.56 to 1.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg PG-760564 BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.666
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 80%; 0.50 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Placebo		25 mg PG-760564 BID		100 mg PG-760564 BID
Arm/Group Description	Placebo, oral dose, BID		25 mg BID, of oral PG-760564		100 mg BID, of oral PG-760564
All Cause Mortality
	Placebo		25 mg PG-760564 BID		100 mg PG-760564 BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		25 mg PG-760564 BID		100 mg PG-760564 BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/85 (1.2%)		4/85 (4.7%)		6/86 (7%)
Gastrointestinal disorders
Haemorrhoids	0/85 (0%)	0	0/85 (0%)	0	1/86 (1.2%)	1
General disorders
Pyrexia	0/85 (0%)	0	0/85 (0%)	0	1/86 (1.2%)	1
Infections and infestations
Pneumonia	0/85 (0%)	0	1/85 (1.2%)	1	1/86 (1.2%)	1
Urosepsis	1/85 (1.2%)	1	0/85 (0%)	0	0/86 (0%)	0
Viral Infection	0/85 (0%)	0	1/85 (1.2%)	1	0/86 (0%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration	0/85 (0%)	0	1/85 (1.2%)	1	0/86 (0%)	0
Rheumatoid Arthritis	0/85 (0%)	0	0/85 (0%)	0	1/86 (1.2%)	1
Psychiatric disorders
Suicide Attempt	0/85 (0%)	0	0/85 (0%)	0	1/86 (1.2%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary granuloma	0/85 (0%)	0	1/85 (1.2%)	1	0/86 (0%)	0
Pulmonary fibrosis	0/85 (0%)	0	0/85 (0%)	0	1/86 (1.2%)	1
Vascular disorders
Deep vein thrombosis	1/85 (1.2%)	1	0/85 (0%)	0	0/86 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		25 mg PG-760564 BID		100 mg PG-760564 BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/85 (3.5%)		2/85 (2.4%)		5/86 (5.8%)
Investigations
Alanine aminotransferase increased	3/85 (3.5%)	4	2/85 (2.4%)	2	5/86 (5.8%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

It will be the Sponsor's responsibility to convene and charter a Publications Committee consisting of representation from the Sponsor and key academic and investigational centers. The Publications Committee will be primarily responsible for the creation, review, and submission of publications and presentations relating to the major aspects of the study (design, baseline data, mortality and safety data) and ancillary analyses after the completion of the study.