Randomised, double-blind, placebo-controlled, parallel-group trial to investigate the analgesic effect of OROS hydromorphone hydrochloride in comparison with placebo in subjects with moderate to severe pain induced by osteoarthritis of the hip or the knee - HOP Trial

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-006911-60-CZ
• Date of registration: 11/05/2007
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• Public title: Randomised, double-blind, placebo-controlled, parallel-group trial to investigate the analgesic effect of OROS hydromorphone hydrochloride in comparison with placebo in subjects with moderate to severe pain induced by osteoarthritis of the hip or the knee - HOP Trial
• Scientific title: Randomised, double-blind, placebo-controlled, parallel-group trial to investigate the analgesic effect of OROS hydromorphone hydrochloride in comparison with placebo in subjects with moderate to severe pain induced by osteoarthritis of the hip or the knee - HOP Trial
• Date of first enrolment: 15/06/2007
• Target sample size: 270
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-006911-60
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Czech Republic, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1) Male or female older than 40 years of age
2) Female subjects must be postmenopausal (for at least one year), surgically sterile, abstinent, or if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilisation) before entry into the study and throughout the study’s duration; women of childbearing potential must have a negative serum beta human chorionic gonadotropin (beta-hCG) pregnancy test at screening, and a negative urine pregnancy test at visit 8 (week 16)
3) Subjects must have signed an informed consent form indicating that they understand the procedures required for the study and their purposes, and are willing to participate in the study
4) Documented OA of the hip or knee (as defined by the American College of Rheumatology [24, 25]), with radiological evidence of OA from the target joint
5) Chronic pain for more than 3 months treated with daily analgesic for the last month
6) Moderate to severe OA pain of the target joint, not adequately controlled with NSAIDs or paracetamol in the month before the beginning of the study
7) The following inclusion criterion will be checked at baseline visit:
Mean weekly score of = 5 (on a scale of 0–10) in the BPI item 5 “pain on average” which will be calculated as a mean of the pain assessments collected at screening visit (week –1), telephone call (week -0,5) and baseline visit (week 0)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1) Regular treatment with an opioid in the 4 weeks before screening visit. (Infrequent use of tramadol, codeine, tilidine, or dihydrocodeine for no more than 10 days in the 4 weeks before the screening visit is acceptable. However, subjects should stop any use of weak opioids at screening visit).
2) History of allergy or hypersensitivity to hydromorphone or other opioid analgesic drugs
3) Diagnosis of major depression
4) Treatment for epilepsy
5) Treatment with sedative hypnotics, anaesthetics, neuroleptics, or muscle relaxants (the exception to this is low dose sedative hypnotics with the sole purpose of helping to aid night rest).
6) Corticosteroid injections in the 3 months before the start of the study
7) Documented or suspected alcohol or drug abuse, or are suspected of having an addictive personality in the investigator’s judgement
8) Another type of continuous pain that stands out in comparison with OA pain such as fibromyalgia, cervical radiculopathy, or chronic low back pain
9) Any of the following in the 6 months before entering the study:
- Major trauma to the target joints
- Infection in the target joints
- Radiologically apparent avascular necrosis in the target joints
- Hyaluronan injections in the target joints
10) Major surgery in the 3 months before the start of the study
11) Arthrodesis in the year or arthroscopy in the 2 months before entering the study
12) Subjects who have started any form of physiotherapy, psychological therapy for pain, massage, use of a transcutaneous electrical nerve stimulation (TENS) machine, acupuncture, or physical therapy in the 3 weeks before the run-in period. Such therapies can continue if they were started more than 3 weeks before the start of the run-in period and must be continued at the same frequency of administration throughout the study and must be recorded on subjects’ case report forms (CRFs)
13) Planned treatment that could alter the degree of pain within the study period
14) Subjects known to have any of the following:
- Chronic obstructive respiratory symptoms or susceptibility to respiratory depression
- Significantly abnormal renal or hepatic function documented in medical records (a significant laboratory result, no older than 6 months for severe renal impairment: twice the upper limit of normal serum creatinine or creatinine clearance < 10 mL/min, or for severe hepatic impairment five times the upper limit of normal serum transaminases [ALT or AST]. In the absence of laboratory data for renal or hepatic function or if data is older than 6 months, the tests should be done at screening)
- Any disease or condition that may compromise the function of those body systems that could result in altered absorption, excess accumulation, impaired metabolism, or impaired excretion of the study drug
15) Received an experimental drug or used an experimental medical device within the 30 days before entering the study
16) Unable to comply with the study assessments and complete the questionnaires
17) Female subjects who are pregnant or breastfeeding
18) Subjects who have had GI resection or this kind of surgery planned during the trial
19) Subjects who are being treated with buprenorphine, nalbuphine, or pentazocine
20) Subjects who are being treated with monoamine oxidase (MAO) inhibitors or if treatment discontinued within 14 days of the start of the study
21) Subjects with acute life-threatening or poorly controlled diseases
22) Relatives of the i

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

moderate to severe pain induced by osteoarthritis of the hip or the knee
MedDRA version: 9.1 Level: LLT Classification code 10003239 Term: Arthralgia

Intervention(s)

Trade Name: Jurnista 8mg
Product Name: OROS hydromorphone hydrochloride
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: hydromorphone hydrochloride
CAS Number: 71-68-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 8-
Pharmaceutical form of the placebo: Prolonged-release tablet
Route of administration of the placebo: Oral use

Product Name: OROS hydromorphone hydrochloride
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: hydromorphone hydrochloride
CAS Number: 71-68-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-
Pharmaceutical form of the placebo: Prolonged-release tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: • To assess the drop-out rate due to adverse events
• To assess the effect of treatment on subjects’ functionality using the total score of the WOMAC OA index
• To assess the effect of treatment on pain using the pain subscales of the WOMAC OA index and the SF-36 and the items 3, 4 and 6 of the BPI
• To assess the effect of treatment on subjects’ HRQoL, which will be assessed using all subscales, except pain, of the instrument SF-36
• To assess the effect of treatment on subjects’ functional impairment and stiffness using these subscales of the WOMAC OA index
• To assess the effect of treatment on subjects’ quality of sleep using a MOS sleep subscale score
• To assess the overall safety and tolerability of the drug by measurement of vital signs and continuous monitoring of adverse events
• To compare the drop-out rate due to adverse events in the active group with drop-out rates observed in other trials that have used a higher starting dose

Primary end point(s): Efficacy will be assessed by recording the subjects’ mean score in the BPI item 5 “pain on average”, which will be recorded at each study visit. This will be recorded at each study visit and analysed using a mixed model for repeated measures (MMRM).

Main Objective: To compare the analgesic effect of OROS hydromorphone hydrochloride with placebo in subjects with moderate to severe pain induced by osteoarthritis (OA) of the hip or knee which has not been adequately controlled by previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or paracetamol. This will be assessed by the Brief Pain Inventory (BPI) item 5 “pain on average”.

Secondary ID(s)

42801PAI3001