A Double-blind Study of Controlled Release OROS Hydromorphone Compared to Placebo in Patients With Chronic Osteoarthritis (OA) Pain

• Sponsor: Mallinckrodt (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00631319
• Collaborator: (none)
• Enrollment: 343
• Arms: 2
• Duration (Months): 16

Study Details

Study Description

Brief Summary

To evaluate the efficacy of OROS Hydromorphone in reducing moderate to severe chronic pain in patients with Osteoarthritis (OA) Pain

Condition or Disease	Intervention/Treatment	Phase
Chronic Pain	Drug: OROS hydromorphone; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 343 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase III, Flexible Dose Titration Followed by a Randomized Double-Blind Study of Controlled Release OROS Hydromorphone HCL Compared to Placebo in Patients With OA Pain
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OROS Hydromorphone OROS hydromorphone tablets administered orally once daily in total daily doses of 12, 16, 24, 32, 40, 48, or 64 mg	Drug: OROS hydromorphone; hydromorphone 12, 16, 24, 32, 40, 48, or 64 mg tablets
Placebo Comparator: Placebo Matching placebo tablets orally once daily (number and dosage of tablets to match the number and dosage of the stable dose of OROS hydromorphone obtained in the Conversion and Titration phase).	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Patient Diary-derived Numeric Rating Scale (NRS) Pain Intensity Change From Baseline to Week 12 or Final Visit of the Double-blind Phase [Baseline, Week 12]

   Participants rate their pain intensity on a numeric rating scale (NRS), where 0=no pain and 10=worst possible pain, in a daily diary. At Week 12 (or final visit), all measurements during the preceding week are averaged, and the mean change from the mean score at baseline is calculated.

Other Outcome Measures

1. Patient Diary-derived Numeric Rating Scale (NRS) Pain Intensity and Change From Baseline by Visit in the Double-blind Phase [Baseline to Week 12]

2. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score and Change From Baseline by Visit in the Double-blind Phase [Baseline to Week 12]

3. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score and Change From Baseline by Visit in the Double-blind Phase [Baseline to Week 12]

4. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score and Change From Baseline by Visit in the Double-blind Phase [Baseline to Week 12]

5. Patient Global Assessment and Change From Baseline by Visit in the Double-blind Phase [Baseline to Week 12]

6. Time to Treatment Failure From Baseline [within 12 weeks from Baseline]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Primary clinic diagnosis of osteoarthritis pain of the hip or of the knee for at least 6 months

• Patients required daily opioid medication to treat their chronic osteoarthritis pain

Exclusion Criteria

• Joint replacement of the hip or of the knee that is the primary source of osteoarthritis Pain

• History drug or alcohol abuse

• Fibromyalgia

• Patients who have major depression or anxiety

• Women who are pregnant or breast feeding

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Mallinckrodt

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mallinckrodt
• ClinicalTrials.gov Identifier: NCT00631319
• Other Study ID Numbers: NMT 1077-302
• First Posted: Mar 7, 2008
• Last Update Posted: Sep 16, 2020
• Last Verified: Aug 1, 2020

• Keywords provided by Mallinckrodt: OA; Chronic Pain; Osteoarthritis; OA Pain; Osteoarthritis Pain; Pain; Hip Pain; Knee Pain; Joint Pain
• Additional relevant MeSH terms: Osteoarthritis; Chronic Pain; Hydromorphone

Study Results

Participant Flow

Arm/Group Title	OROS Hydromorphone	Placebo
Arm/Group Description	OROS hydromorphone tablets administered orally once daily in total daily doses of 12, 16, 24, 32, 40, 48, or 64 mg	Matching placebo tablets orally once daily
Period Title: Conversion and Titration Phase
STARTED	343	0
COMPLETED	200	0
NOT COMPLETED	143	0
Period Title: Conversion and Titration Phase
STARTED	100	100
COMPLETED	60	65
NOT COMPLETED	40	35

Baseline Characteristics

Arm/Group Title	OROS Hydromorphone	Placebo	Total
Arm/Group Description	OROS hydromorphone tablets administered orally once daily in total daily doses of 12, 16, 24, 32, 40, 48, or 64 mg	Matching placebo tablets orally once daily	Total of all reporting groups
Overall Participants	100	100	200
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	83 83%	77 77%	160 80%
>=65 years	17 17%	23 23%	40 20%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.3 (9.78)	55.4 (11.1)	55.8 (10.44)
Sex: Female, Male (Count of Participants)
Female	54 54%	53 53%	107 53.5%
Male	46 46%	47 47%	93 46.5%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	100 100%	100 100%	200 100%

Outcome Measures

1. Primary Outcome

Title	Patient Diary-derived Numeric Rating Scale (NRS) Pain Intensity Change From Baseline to Week 12 or Final Visit of the Double-blind Phase
Description	Participants rate their pain intensity on a numeric rating scale (NRS), where 0=no pain and 10=worst possible pain, in a daily diary. At Week 12 (or final visit), all measurements during the preceding week are averaged, and the mean change from the mean score at baseline is calculated.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent to treat population defined as all patients randomized to the Double-blind phase who received at least one dose of randomized study medication.

Arm/Group Title	OROS Hydromorphone	Placebo
Arm/Group Description	OROS hydromorphone tablets administered orally once daily in total daily doses of 12, 16, 24, 32, 40, 48, or 64	Matching placebo tablets orally once daily
Measure Participants	100	100
Mean (Standard Deviation) [units on a scale]	0.6 (2.02)	0.6 (1.87)

2. Other Pre-specified Outcome

Title	Patient Diary-derived Numeric Rating Scale (NRS) Pain Intensity and Change From Baseline by Visit in the Double-blind Phase
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Other Pre-specified Outcome

Title	Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score and Change From Baseline by Visit in the Double-blind Phase
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Other Pre-specified Outcome

Title	Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score and Change From Baseline by Visit in the Double-blind Phase
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Other Pre-specified Outcome

Title	Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score and Change From Baseline by Visit in the Double-blind Phase
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Patient Global Assessment and Change From Baseline by Visit in the Double-blind Phase
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Time to Treatment Failure From Baseline
Time Frame	within 12 weeks from Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Duration of the trial: 1 year, 4 months
Adverse Event Reporting Description	The safety population includes all patients who were enrolled and who took at least one dose of study drug (N=338). Adverse event displays include data from the safety population. The number of subjects who entered the Conversion and Titration phase was 343.
Arm/Group Title	Conversion and Titration Phase		Double-blind Phase - Hydromorphone		Double-blind Phase - Placebo
Arm/Group Description	OROS hydromorphone 12, 16, 24, 32, 40, 48 or 64 mg		OROS hydromorphone 12, 16, 24, 32, 40, 48 or 64 mg		Matching placebo tablets orally once daily
All Cause Mortality
	Conversion and Titration Phase		Double-blind Phase - Hydromorphone		Double-blind Phase - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Conversion and Titration Phase		Double-blind Phase - Hydromorphone		Double-blind Phase - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/338 (1.8%)		5/100 (5%)		1/100 (1%)
Cardiac disorders
Cardiac failure congestive	1/338 (0.3%)		0/100 (0%)		0/100 (0%)
Gastrointestinal disorders
Abdominal pain upper	0/338 (0%)		1/100 (1%)		0/100 (0%)
Gastroenteritis	0/338 (0%)		1/100 (1%)		0/100 (0%)
Inguinal hernia	1/338 (0.3%)		0/100 (0%)		0/100 (0%)
Pancreatitis acute	0/338 (0%)		1/100 (1%)		0/100 (0%)
General disorders
Oedema peripheral	1/338 (0.3%)		0/100 (0%)		0/100 (0%)
Hepatobiliary disorders
Cholelithiasis	1/338 (0.3%)		0/100 (0%)		0/100 (0%)
Infections and infestations
Pneumonia	1/338 (0.3%)		1/100 (1%)		0/100 (0%)
Septic shock	1/338 (0.3%)		0/100 (0%)		0/100 (0%)
Urinary tract infection	0/338 (0%)		0/100 (0%)		1/100 (1%)
Injury, poisoning and procedural complications
Drug toxicity	1/338 (0.3%)		0/100 (0%)		0/100 (0%)
Musculoskeletal and connective tissue disorders
Chest pain	0/338 (0%)		1/100 (1%)		0/100 (0%)
Psychiatric disorders
Completed suicide	1/338 (0.3%)		0/100 (0%)		0/100 (0%)
Renal and urinary disorders
Urethral caruncle	1/338 (0.3%)		0/100 (0%)		0/100 (0%)
Vascular disorders
Embolism	0/338 (0%)		1/100 (1%)		0/100 (0%)
Other (Not Including Serious) Adverse Events
	Conversion and Titration Phase		Double-blind Phase - Hydromorphone		Double-blind Phase - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	197/338 (58.3%)		68/100 (68%)		52/100 (52%)
Gastrointestinal disorders
Abdominal pain upper	0/338 (0%)		7/100 (7%)		1/100 (1%)
Constipation	59/338 (17.5%)		20/100 (20%)		4/100 (4%)
Diarrhoea	0/338 (0%)		6/100 (6%)		7/100 (7%)
Dry mouth	0/338 (0%)		2/100 (2%)		0/100 (0%)
Food poisoning	0/338 (0%)		2/100 (2%)		0/100 (0%)
Nausea	53/338 (15.7%)		14/100 (14%)		5/100 (5%)
Toothache	0/338 (0%)		2/100 (2%)		0/100 (0%)
Vomiting	19/338 (5.6%)		9/100 (9%)		5/100 (5%)
General disorders
Drug withdrawal syndrome	15/338 (4.4%)		5/100 (5%)		8/100 (8%)
Fatigue	11/338 (3.3%)		2/100 (2%)		1/100 (1%)
Oedema peripheral	10/338 (3%)		4/100 (4%)		1/100 (1%)
Pyrexia	0/338 (0%)		2/100 (2%)		3/100 (3%)
Infections and infestations
Bronchitis	0/338 (0%)		0/100 (0%)		3/100 (3%)
Gastroenteritis	0/338 (0%)		4/100 (4%)		0/100 (0%)
Influenza	0/338 (0%)		2/100 (2%)		3/100 (3%)
Nasopharyngitis	0/338 (0%)		4/100 (4%)		2/100 (2%)
Sinusitis	9/338 (2.7%)		3/100 (3%)		2/100 (2%)
Tooth abscess	0/338 (0%)		0/100 (0%)		3/100 (3%)
Upper respiratory tract infection	7/338 (2.1%)		4/100 (4%)		2/100 (2%)
Urinary tract infection	0/338 (0%)		3/100 (3%)		3/100 (3%)
Injury, poisoning and procedural complications
Contusion	0/338 (0%)		2/100 (2%)		1/100 (1%)
Investigations
Blood alkaline phosphatase increased	0/338 (0%)		2/100 (2%)		0/100 (0%)
Weight decreased	0/338 (0%)		3/100 (3%)		2/100 (2%)
Metabolism and nutrition disorders
Arthralgia	7/338 (2.1%)		7/100 (7%)		3/100 (3%)
Musculoskeletal and connective tissue disorders
Back pain	9/338 (2.7%)		2/100 (2%)		2/100 (2%)
Joint stiffness	3/338 (0.9%)		2/100 (2%)		1/100 (1%)
Joint swelling	0/338 (0%)		0/100 (0%)		2/100 (2%)
Musculoskeletal pain	0/338 (0%)		0/100 (0%)		2/100 (2%)
Myalgia	0/338 (0%)		2/100 (2%)		0/100 (0%)
Neck pain	0/338 (0%)		2/100 (2%)		0/100 (0%)
Osteoarthritis	0/338 (0%)		0/100 (0%)		2/100 (2%)
Nervous system disorders
Dizziness	15/338 (4.4%)		4/100 (4%)		0/100 (0%)
Headache	22/338 (6.5%)		5/100 (5%)		7/100 (7%)
Somnolence	28/338 (8.3%)		1/100 (1%)		2/100 (2%)
Tremor	0/338 (0%)		2/100 (2%)		0/100 (0%)
Psychiatric disorders
Anxiety	0/338 (0%)		0/100 (0%)		2/100 (2%)
Insomnia	0/338 (0%)		3/100 (3%)		1/100 (1%)
Respiratory, thoracic and mediastinal disorders
Cough	0/338 (0%)		0/100 (0%)		2/100 (2%)
Rhinorrhea	0/338 (0%)		3/100 (3%)		1/100 (1%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	8/338 (2.4%)		2/100 (2%)		1/100 (1%)
Pruritus	11/338 (3.3%)		3/100 (3%)		1/100 (1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.