Trial Outcomes & Findings for Efficacy and Safety Study of HZT-501 in Reducing the Risk of Ibuprofen-associated Ulcers (NCT NCT00450658)

Last Updated: 2024-12-16

Results Overview

The primary efficacy endpoint was the number of subjects with upper gastrointestinal (i.e., gastric and/or duodenal) ulcer at any time throughout 24 weeks of treatment. An ulcer was defined as a mucosal break of at least 3 mm in diameter with unequivocal depth. A subject is considered to have completed the study if all scheduled assessments up through the Week 24 visit have been performed.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

627 participants

Primary outcome timeframe

24 weeks

Results posted on

2024-12-16

Participant Flow

A multi-center US study in which 80 sites recruited subjects between March 2007 and February 2008.

Following screening for eligibility and wash-out of restricted medications, subjects were assigned according to the treatment to which they were randomized in a 2:1 ratio (HZT-501:ibuprofen).

Participant milestones

Participant milestones
Measure	HZT-501 HZT-501: Ibuprofen 800mg/Famotidine 26.6mg tablets t.i.d.	Ibuprofen Ibuprofen 800mg tablets t.i.d.
Overall Study STARTED	415	212
Overall Study COMPLETED	272	122
Overall Study NOT COMPLETED	143	90

Reasons for withdrawal

Reasons for withdrawal
Measure	HZT-501 HZT-501: Ibuprofen 800mg/Famotidine 26.6mg tablets t.i.d.	Ibuprofen Ibuprofen 800mg tablets t.i.d.
Overall Study Adverse Event	24	15
Overall Study Withdrawal by Subject	43	26
Overall Study Lost to Follow-up	22	5
Overall Study UGI ulcer	33	34
Overall Study misc	21	10

Baseline Characteristics

Efficacy and Safety Study of HZT-501 in Reducing the Risk of Ibuprofen-associated Ulcers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HZT-501 n=415 Participants HZT-501: Ibuprofen 800mg/Famotidine 26.6mg	Ibuprofen n=212 Participants Ibuprofen 800mg	Total n=627 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	342 Participants n=5 Participants	173 Participants n=7 Participants	515 Participants n=5 Participants
Age, Categorical >=65 years	73 Participants n=5 Participants	39 Participants n=7 Participants	112 Participants n=5 Participants
Age, Continuous	55.3 years STANDARD_DEVIATION 9.0 • n=5 Participants	55.7 years STANDARD_DEVIATION 9.5 • n=7 Participants	55.4 years STANDARD_DEVIATION 9.1 • n=5 Participants
Sex: Female, Male Female	272 Participants n=5 Participants	152 Participants n=7 Participants	424 Participants n=5 Participants
Sex: Female, Male Male	143 Participants n=5 Participants	60 Participants n=7 Participants	203 Participants n=5 Participants
Region of Enrollment United States	415 participants n=5 Participants	212 participants n=7 Participants	627 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination and at least the Week 8 endoscopic examination.

Outcome measures

Outcome measures
Measure	HZT-501 n=380 Participants HZT-501: Ibuprofen 800mg/Famotidine 26.6mg	Ibuprofen n=190 Participants Ibuprofen 800mg
Number of Subjects Who Develop Endoscopically-diagnosed Upper Gastrointestinal Ulcers Confirmed by Endoscopy.	40 participants Interval 3.0 to 15.9	38 participants Interval 3.0 to 15.9

SECONDARY outcome

Timeframe: 24 weeks

Population: The secondary efficacy endpoint was the number of subjects with gastric ulcer at any time throughout 24 weeks of treatment. An ulcer was defined as a mucosal break of at least 3 mm in diameter with unequivocal depth. A subject is considered to have completed the study if all scheduled assessments up through the Week 24 visit were performed.

The secondary efficacy endpoint was the number of subjects with gastric ulcer at any time throughout 24 weeks of treatment. An ulcer was defined as a mucosal break of at least 3 mm in diameter with unequivocal depth. A subject is considered to have completed the study if all scheduled assessments up through the Week 24 visit have been performed.

Outcome measures

Outcome measures
Measure	HZT-501 n=380 Participants HZT-501: Ibuprofen 800mg/Famotidine 26.6mg	Ibuprofen n=190 Participants Ibuprofen 800mg
Number of Subjects Who Develop Endoscopically-diagnosed Gastric Ulcers During the 24-week Treatment Period.	37 participants Interval 1.9 to 14.4	34 participants Interval 1.9 to 14.4

SECONDARY outcome

Timeframe: 24 weeks

The secondary efficacy endpoint was the number of subjects with duodenal ulcer at any time throughout the 24 weeks of treatment. An ulcer was defined as a mucosal break of at least 3 mm in diameter with unequivocal depth. A subject is considered to have completed the study if all scheduled assessments up through the Week 24 visit have been performed.

Outcome measures

Outcome measures
Measure	HZT-501 n=380 Participants HZT-501: Ibuprofen 800mg/Famotidine 26.6mg	Ibuprofen n=190 Participants Ibuprofen 800mg
Number of Subjects Who Develop Endoscopically-diagnosed Duodenal Ulcers During the 24-week Treatment Period.	3 participants Interval 0.8 to 7.1	9 participants Interval 0.8 to 7.1

SECONDARY outcome

Timeframe: 24 weeks

Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic exam. Subjects were assigned according to the treatment to which they received.

The secondary efficacy endpoint was the number of subjects developing a NSAID-associated serious GI complication at any time throughout 6 months of treatment. A NSAID-associated serious GI complication was defined as a perforation of ulcers, gastric outlet obstruction due to ulcers, and/or GI bleeding.

Outcome measures

Outcome measures
Measure	HZT-501 n=415 Participants HZT-501: Ibuprofen 800mg/Famotidine 26.6mg	Ibuprofen n=212 Participants Ibuprofen 800mg
The Incidence Rate of NSAID-associated Serious Gastrointestinal Complications.	0 participants	0 participants

Adverse Events

HZT-501

Serious events: 11 serious events

Other events: 220 other events

Deaths: 0 deaths

Ibuprofen

Serious events: 4 serious events

Other events: 116 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Amy Grahn, MS Senior Vice President, Clinical Development and Operations

Horizon Pharma, Inc.

Phone: 224-383-3012

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI reserves the right to publish or otherwise make public the Study results provided that such communication occurs only after (i) the results of the multicenter Study in its entirety have been publicly disclosed by, or with consent of the sponsor or (ii) 18 months after conclusion of the Study at all sites, whichever comes first. Following this, PI can publish, present or use any non-confidential study results following Sponsor review. PI will not make public raw data or Case Reports.
Publication restrictions are in place

Restriction type: OTHER

Measure	HZT-501 n=415 participants at risk HZT-501: Ibuprofen 800mg/Famotidine 26.6mg	Ibuprofen n=212 participants at risk Ibuprofen 800mg
Infections and infestations abscess	0.24% 1/415 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.00% 0/212 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
Respiratory, thoracic and mediastinal disorders asthma	0.24% 1/415 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.00% 0/212 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
Respiratory, thoracic and mediastinal disorders bronchospasm	0.24% 1/415 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.00% 0/212 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
General disorders chest pain	0.24% 1/415 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.00% 0/212 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
Respiratory, thoracic and mediastinal disorders chronic obstructive pulmonary disease	0.24% 1/415 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.00% 0/212 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
Cardiac disorders coronary artery disease	0.00% 0/415 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.47% 1/212 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
Infections and infestations diverticulitis	0.24% 1/415 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.00% 0/212 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
General disorders edema peripheral	0.00% 0/415 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.47% 1/212 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
Gastrointestinal disorders esophageal ulcer	0.24% 1/415 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.00% 0/212 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
Infections and infestations infection	0.24% 1/415 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.00% 0/212 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
Gastrointestinal disorders inguinal hernia	0.24% 1/415 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.00% 0/212 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
General disorders non-cardiac chest pain	0.24% 1/415 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.47% 1/212 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
Musculoskeletal and connective tissue disorders osteoarthritis	0.24% 1/415 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.00% 0/212 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
Musculoskeletal and connective tissue disorders osteonecrosis	0.00% 0/415 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.47% 1/212 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
Musculoskeletal and connective tissue disorders rotator cuff syndrome	0.24% 1/415 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.00% 0/212 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
Psychiatric disorders schizoaffective disorder	0.24% 1/415 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.00% 0/212 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
Psychiatric disorders suicide attempt	0.24% 1/415 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.00% 0/212 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
Nervous system disorders transient ischemic attack	0.24% 1/415 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.00% 0/212 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.
Injury, poisoning and procedural complications wrist fracture	0.24% 1/415 • Number of events 1 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.	0.00% 0/212 • Randomization through 24 weeks. Safety Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination. Subjects were assigned to the treatment to which they received; 2:1 randomization, HZT-501:ibuprofen.