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

Phase 2

Completed

• Conditions: Osteoarthrosis
• Interventions: Drug: 20 mg of Hydrocodone Bitartrate Extended Release (HC-ER); Drug: 10 mg of Hydrocodone Bitartrate Extended Release (HC-ER)

• Registration Number: NCT02222740
• Lead Sponsor: Zogenix, Inc.

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

Study Timeline

• Study Start: 2002-09
• Primary Completion: 2002-12
• Study Completion: 2002-12
• Study First Submitted: 2014-07-21
• Status Verified: 2014-08
• Study First Submitted QC: 2014-08-19
• Study First Posted: 2014-08-21
• Last Update Submitted: 2022-11-08
• Last Update Posted: 2022-11-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 2	20 mg of Hydrocodone Bitartrate Extended Release (HC-ER)	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
Group 1	10 mg of Hydrocodone Bitartrate Extended Release (HC-ER)	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

Primary Outcome Measures

Name	Time	Method
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.