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

NCT02222740 | Completed Phase 2

• 1 other identifier: ELN154088-203
• Study Type: interventional
• Target: 37
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Osteoarthrosis

Keywords

Safety; Tolerability; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Group 1

EXPERIMENTAL

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)

Group 2

EXPERIMENTAL

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)

Interventions

10 mg of Hydrocodone Bitartrate Extended Release (HC-ER) DRUG

Schedule II Class

Also known as: Zohydro ER

Group 1

20 mg of Hydrocodone Bitartrate Extended Release (HC-ER) DRUG

Schedule II Class

Also known as: Zohydro ER

Group 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zogenix, Inc.: lead

MeSH Terms

Conditions

Osteoarthritis

Interventions

Hydrocodone

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2014
• First Posted: August 21, 2014
• Study Start: September 1, 2002
• Primary Completion: December 1, 2002
• Study Completion: December 1, 2002
• Last Updated: November 10, 2022

Record last verified: 2014-08