Osteoarthrosis
Conditions
Keywords
Safety, Tolerability, Pharmacokinetics
Brief summary
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
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
Interventions
DRUG10 mg of Hydrocodone Bitartrate Extended Release (HC-ER)
Schedule II Class
DRUG20 mg of Hydrocodone Bitartrate Extended Release (HC-ER)
Schedule II Class
Sponsors
Zogenix, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess the steady-state pharmacokinetics (PK) of multiple dose of 10, 20, 30, and 40 mg of HC-ER | Day 1-28 | 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. |
Outcome results
None listed