A Safety, Tolerability and Pharmacokinetic Dose Escalation Study of HC-ER in Patients With Osteoarthritis Pain

Study Overview
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Brief Summary
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Assess the safety, tolerability and pharmacokinetics of multiple doses of 10, 20, 30, and 40 mg of Hydrocodone Bitartrate Extended Release (HC-ER)capsules taken with food at steady state, in subjects with chronic, moderate to severe osteoarthritis (OA) pain.

Detailed Description
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Safety parameters assessed included adverse events, physical examinations, vital signs, 12-lead electrocardiogram (ECGs), clinical laboratory testing and overall Arthritis Pain Intensity and opioid side effects

Official Title
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A Multiple-Dose, Safety, Tolerability, and Pharmacokinetic Dose-Escalation Study of Hydrocodone Bitartrate Extended Release (HC-ER) in Patients With Chronic, Moderate to Severe Osteoarthritis Pain

Conditions
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Osteoarthrosis

Intervention / Treatment
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* Drug: 10 mg of Hydrocodone Bitartrate Extended Release (HC-ER)
* Drug: 20 mg of Hydrocodone Bitartrate Extended Release (HC-ER)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects were 18 years or older Subjects had osteoarthritis (OA) defined by: Presence of of typical hip and/or knee joint symptoms. Involvement of at least 1 hip or knee joints that had warranted treatment with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), including cyclooxygenase-2 [COX-2] inhibitors and/or acetaminophen (APAP) for the last 3 months. Radiographic evidence within the last 6 months of OA in the index joint, with Grade II to IV severity, as illustrated by the Atlas of Standard Radiographs. Subjects were otherwise in generally good health, as determined by the investigator, on the basis of medical history, physical examination, electrocardiogram (ECG), and screening laboratory results. Female subjects were either physically incapable of childbearing or were practicing an acceptable method of birth control and had a negative pregnancy test result demonstrated before dosing. Subjects had experienced a suboptimal response to APAP and NSAID therapy (including COX-2 inhibitor). Subjects had used opioids for OA pain on an as needed (PRN) or occasional basis. Subjects were willing and able to discontinue or modify their current medication used for management of OA pain per protocol. Subjects had steady, not transient, pain and a categorical pain rating of moderate to severe on a scale of none, mild, moderate, or severe. Subjects weighed > or = to100 lbs. If a subject had taken any inducers or inhibitors of cytochrome P450 [CYP450j), these were discontinued and an appropriate washout period (5 half-lives) had occurred before entry in the study. Subjects were able to take oral medication and were willing to comply with the protocol. Subjects agreed to abstain from alcohol consumption for the duration of the study. Subjects were able to read, understand, and voluntarily sign the IRB approved consent document before the performance of any study-specific procedures. Exclusion Criteria: Subjects had any clinically significant condition that would, in the investigator's opinion, preclude study participation. Subjects had any other clinically significant form of disease at the index joint (study joint) or had been diagnosed with inflammatory arthritis, gout, pseudo-gout, Paget's disease, or any other chronic pain syndrome that, in the investigator's opinion, might interfere with the assessment of pain and other symptoms of OA. Subjects had known allergies or previous, significant reactions to opioids. Subjects had any laboratory abnormality at screening that was considered clinically significant by the investigator, or that, in the opinion of the investigator, would have contraindicated study participation. Subjects were known to have positive test results for human immunodeficiency virus (HIV), hepatitis B antigen, or hepatitis C antibody. Subjects had a history of chronic, scheduled opioid use for OA. Subjects had any signs or symptoms of opioid withdrawal. Subjects had a history of substance or alcohol abuse within 2 years before study entry. Subjects tested positively on a urine screen for drugs of abuse. Subjects had received any steroid therapy (e.g., oral, intramuscular, intravenous, or soft tissue) within 1 month of study entry. Subjects had a condition that would contraindicate the use of opioid analgesia. Subjects had participated in a study of an investigational drug or device, or had donated blood, within 30 days before study entry. Subjects used any medication that the investigator felt would interact unfavorably with the study medication (e.g., potentiation of sedation with tricyclic antidepressants). Subjects had used opioid analgesics for more than 3 days during the 30 days before screening. Subjects had a history of seizures. Subjects were considered by the investigator to be unsuitable for any reason.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>10 mg of Hydrocodone Bitartrate Extended Release (HC-ER) Twice per day (BID) for 7 days, followed by 20 mg BID for 7 days, followed by 30 mg BID for 7 days | Drug: 10 mg of Hydrocodone Bitartrate Extended Release (HC-ER)<br>* Schedule II Class<br>* Other names: Zohydro ER;|
| Experimental: Group 2<br>20 mg of Hydrocodone Bitartrate Extended Release (HC-ER) Twice Per Day (BID) for 7 days, followed by 30 mg BID for 7 days, followed by 40 mg BID for 7 days | Drug: 20 mg of Hydrocodone Bitartrate Extended Release (HC-ER)<br>* Schedule II Class<br>* Other names: Zohydro ER;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the steady-state pharmacokinetics (PK) of multiple dose of 10, 20, 30, and 40 mg of HC-ER | PK parameters including Tmax, Cmax and Cmin were calculated for each dose level in each group from the PK profile of hydrocodone and the metabolites hydromorphone, and norhydrocodone. | Day 1-28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Tolerability, Pharmacokinetics