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

Osteoarthrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02222740
• Other study ID #: ELN154088-203
• Status: Completed
• Phase: Phase 2
• Start date: September 2002
• Est. completion date: December 2002

Study information

• Verified date: August 2014
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: December 2002
• Est. primary completion date: December 2002
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthrosis

Intervention

Drug:
• 10 mg of Hydrocodone Bitartrate Extended Release (HC-ER)
Schedule II Class
• 20 mg of Hydrocodone Bitartrate Extended Release (HC-ER)
Schedule II Class

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Zogenix, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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