A 12-month, Phase 3, Open-label, Multi-center Study to Evaluate the Long-term Safety of PN400 (VIMOVO)

• Sponsor: POZEN (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00527904
• Collaborator: (none)
• Enrollment: 239
• Location: 1
• Arm: 1
• Duration (Months): 24
• Patients Per Site Per Month: 10

Study Details

Study Description

Brief Summary

This study uses an open-label design and will be conducted in approximately 60 sites aiming to enroll a total number of 200 subjects to ensure that at least 100 subjects will have 12 months exposure to PN400 (VIMOVO).

Condition or Disease	Intervention/Treatment	Phase
Gastric Ulcer	Drug: PN400 (VIMOVO); Drug: PN 400 (VIMOVO)	Phase 3

Detailed Description

PN400 is proposed for the treatment of the signs and symptoms of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis or other medical conditions expected to require daily NSAID therapy for at least 12 months in patients at risk for developing NSAID-associated gastric ulcers. This study is designed to provide long-term safety data for PN400 in order to gain regulatory approval to make PN400 available for clinical use in this subject population.

Study Design

• Study Type: Interventional
• Actual Enrollment: 239 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 12-month, Phase 3, Open-label, Multi-center Study to Evaluate the Long-term Safety of PN400 in Subjects Who Are at Risk for Developing NSAID-associated Ulcers
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Experimental: PN 400 (VIMOVO) 500 mg delayed release naproxen/20 mg immediate release esomeprazole

Drug: PN400 (VIMOVO); Subjects are instructed to take 2 tablets a day, one in the morning and one in the afternoon/evening. The morning tablet should be taken with water, on an empty stomach 30 to 60 minutes before breakfast, or the first meal. The afternoon/evening tablet should be taken with water, on an empty stomach 30 to 60 minutes before dinner. Tablets should be swallowed whole and not broken, crushed or chewed.; Other Names: Naprosyn Nexium ; Drug: PN 400 (VIMOVO); 500 mg delayed-release naproxen/20 mg immediate release esomperazole dosed twice daily for 12 months; Other Names: Naprosyn Nexium

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Monitored for Long-term Safety of PN 400 [12 months]

   Incidence of adverse events and monitoring vital signs, clinical laboratory values, physical exams, ECG. All AEs were coded into preferred terms according to MedDRA (Medical Dictionary for Regulatory Activities) and classified by system organ class (SOC). Summaries of the incidence of all treatment-emergent AEs, treatment-related AEs, SAEs, and AEs leading to study drug discontinuation were prepared. Treatment-emergent AEs were also summarized by maximum severity, by quartile of number of doses taken and by treatment window.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

A subject was eligible for inclusion in this study if all of the following criteria applied:

1. Male or non-pregnant female subjects with a history of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis or other medical conditions expected to require daily NSAID therapy for at least 12 months:

who were

• 18-49 years of age and had a history of a documented, uncomplicated gastric or duodenal ulcer (a mucosal break of at least 3 mm in diameter with depth, without any concurrent bleeding, clot or perforation) within the past 5 years or, who were

• 50 years of age and older (These subjects did not require a history of a documented, uncomplicated gastric or duodenal ulcer within the past 5 years).

1. Female subjects were eligible for participation in the study if they were of

• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant);

• Childbearing potential, had negative pregnancy test at Screening, and at least 1 of the following applied or was agreed to by the subject:

• Female sterilization or sterilization of male partner; or,

• Hormonal contraception by oral route, implant, injectable, vaginal ring; or,

• Any intrauterine device with published data showing that the lowest expected failure rate is less than 1% per year; or,

• Double barrier method (2 physical barriers or 1 physical barrier plus spermicide); or

• Any other method with published data showing that the lowest expected failure rate is less than 1% per year

1. Each subject was required to be able and willing to provide written informed consent prior to any study procedures being performed.

Exclusion Criteria

A subject was not eligible for inclusion in this study if any 1 or more of the following criteria applied:

1. History of hypersensitivity to esomeprazole or to another PPI

2. History of allergic reaction or intolerance to any NSAID (including aspirin) and/or a history of NSAID-induced symptoms of asthma, rhinitis, and/or nasal polyps

3. Participation in any study of an investigational treatment in the 4 weeks before Screening

4. Presence of uncontrolled acute or chronic medical illness, e.g., GI disorder, hypertension, diabetes, thyroid disorder, depression and/or infection that would have endangered a subject if he/she were to participate in the study

5. GI disorder or surgery leading to impaired drug absorption

6. Evidence of uncontrolled or unstable cardio- or cerebrovascular disorder which in the investigator's opinion would have endangered a subject if he/she were to participate in the study

7. Schizophrenia or bipolar disorder

8. Use of any excluded concomitant medication

9. A recent history (in the past 3 months) suggestive of alcohol or drug abuse or dependence, including overuse/abuse of narcotics for management of pain

10. Serious blood coagulation disorder, including use of systemic anticoagulants

11. Positive test result for Helicobacter pylori at Screening

12. Baseline endoscopy showing any gastric or duodenal ulcer at least 3 mm in diameter with depth

13. Screening laboratory value for any of the following tests that was > 2 times the upper limit of normal: alanine aminotransferase (ALT) and aspartate aminotransferase (AST)

14. Estimated creatinine clearance < 50 mL/min

15. Other than noted specifically, any screening laboratory value that was clinically significant in the investigator's opinion and would have endangered a subject if the subject were to participate in the study

16. History of malignancy, treated or untreated, within the past 5 years, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	POZEN	Chapel Hill	North Carolina	United States	27519

Sponsors and Collaborators

• POZEN

Investigators

• Study Chair: Everardus Orlemans, PhD, POZEN

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00527904
• Other Study ID Numbers: PN400-304
• First Posted: Sep 11, 2007
• Last Update Posted: Aug 31, 2010
• Last Verified: Aug 1, 2010

• Keywords provided by , ,: osteoarthritis; rheumatoid arthritis; ankylosing spondylisit; NSAIDS
• Additional relevant MeSH terms: Stomach Ulcer; Naproxen; Esomeprazole

Study Results

Participant Flow

Recruitment Details	Multi-center US study, 58 sites recruited between October 2007 and March 2009
Pre-assignment Detail	Screening for eligibility and wash-out of restricted medications

Arm/Group Title	PN400 (VIMOVO)
Arm/Group Description	PN 400 (20 mg esomeprazole and 500 mg naproxen) dosed twice daily
Period Title: Overall Study
STARTED	239
COMPLETED	143
NOT COMPLETED	96

Baseline Characteristics

Arm/Group Title	PN400 (VIMOVO)
Arm/Group Description	PN 400 (20 mg esomeprazole and 500 mg naproxen) dosed twice daily
Overall Participants	239
Age (Count of Participants)
<=18 years	0 (0) 0%
Between 18 and 65 years	161 (67.4) 67.4%
>=65 years	78 (32.6) 32.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.8 (8.64)
Sex: Female, Male (Count of Participants)
Female	168 70.3%
Male	71 29.7%
Region of Enrollment (participants) [Number]
United States	239 100%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Monitored for Long-term Safety of PN 400
Description	Incidence of adverse events and monitoring vital signs, clinical laboratory values, physical exams, ECG. All AEs were coded into preferred terms according to MedDRA (Medical Dictionary for Regulatory Activities) and classified by system organ class (SOC). Summaries of the incidence of all treatment-emergent AEs, treatment-related AEs, SAEs, and AEs leading to study drug discontinuation were prepared. Treatment-emergent AEs were also summarized by maximum severity, by quartile of number of doses taken and by treatment window.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Approximately 200 subjects were planned, 239 were enrolled and treated and 143 subjects completed the study. All 239 subjects were evaluable for safety.

Arm/Group Title	PN400 (VIMOVO)
Arm/Group Description	PN 400 (20 mg esomeprazole and 500 mg naproxen) dosed twice daily
Measure Participants	239
Number [participants]	239 100%

Adverse Events

Time Frame	Randomization through 1 year
Arm/Group Title	PN400 (VIMOVO)
Arm/Group Description	PN 400 (20 mg esomeprazole and 500 mg naproxen) dosed twice daily
All Cause Mortality
	PN400 (VIMOVO)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	PN400 (VIMOVO)
	Affected / at Risk (%)	# Events
Total	13/239 (5.4%)
Cardiac disorders
Atrial fibrillation	1/239 (0.4%)	1
Atrioventricular block complete	1/239 (0.4%)	1
Coronary artery disease	1/239 (0.4%)	1
Gastrointestinal disorders
Hematemesis	1/239 (0.4%)	1
General disorders
Non-cardiac chest pain	1/239 (0.4%)	1
Infections and infestations
Pneumonia	2/239 (0.8%)	2
Necrotizing fasciitis	1/239 (0.4%)	1
Staphylococcal infection	1/239 (0.4%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/239 (0.4%)	1
Osteoarthritis	1/239 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer	1/239 (0.4%)	1
Nervous system disorders
Carotid artery stenosis	1/239 (0.4%)	1
Transient ischemic attack	1/239 (0.4%)	1
Psychiatric disorders
Confusional state	1/239 (0.4%)	1
Other (Not Including Serious) Adverse Events
	PN400 (VIMOVO)
	Affected / at Risk (%)	# Events
Total	175/239 (73.2%)
Gastrointestinal disorders
Dyspepsia	19/239 (7.9%)	19
Abdominal pain upper	7/239 (2.9%)	7
Constipation	14/239 (5.9%)	14
Nausea	12/239 (5%)	12
Abdominal pain lower	11/239 (4.6%)	11
Diarrhoea	11/239 (4.6%)	11
Abdominal distension	6/239 (2.5%)	6
Flatulence	5/239 (2.1%)	5
Vomiting	5/239 (2.1%)	5
General disorders
Edema peripheral	11/239 (4.6%)	11
Infections and infestations
Upper respiratory tract infection	14/239 (5.9%)	14
Bronchitis	9/239 (3.8%)	9
Sinusitis	7/239 (2.9%)	7
Urinary tract infection	6/239 (2.5%)	6
Influenza	5/239 (2.1%)	5
Injury, poisoning and procedural complications
Contusion	8/239 (3.3%)	8
Musculoskeletal and connective tissue disorders
Arthralgia	11/239 (4.6%)	11
Back pain	10/239 (4.2%)	10
Osteoarthritis	9/239 (3.8%)	9
Pain in extremity	5/239 (2.1%)	5
Nervous system disorders
Headache	6/239 (2.5%)	6
Dizziness	5/239 (2.1%)	5
Respiratory, thoracic and mediastinal disorders
Cough	6/239 (2.5%)	6
Vascular disorders
Hypertension	9/239 (3.8%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

PI agrees that the first publication will be a multi-center publication of the study results. Following this multi-center publication, PI can publish, present or use any non-confidential study results following Sponsor review and comment.