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

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

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.

Study Overview

• Status: Completed
• Conditions: Osteoarthrosis
• Intervention / Treatment: Drug: 10 mg of Hydrocodone Bitartrate Extended Release (HC-ER); Drug: 20 mg of Hydrocodone Bitartrate Extended Release (HC-ER)

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 Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; 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); Schedule II Class; Other Names: Zohydro ER
Experimental: Group 2; 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); Schedule II Class; Other Names: Zohydro ER

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zogenix, Inc.

Study record dates

Study Major Dates

• Study Start: September 1, 2002
• Primary Completion (Actual): December 1, 2002
• Study Completion (Actual): December 1, 2002

Study Registration Dates

• First Submitted: July 21, 2014
• First Submitted That Met QC Criteria: August 19, 2014
• First Posted (Estimate): August 21, 2014

Study Record Updates

• Last Update Posted (Actual): November 10, 2022
• Last Update Submitted That Met QC Criteria: November 8, 2022
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Tolerability
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Hydrocodone
• Other Study ID Numbers: ELN154088-203