Safety and Pharmacokinetic Study of ALO-02 in Children Ages 7-17 With Pain
- Conditions
- Moderate-severe Pain
- Interventions
- Drug: ALO-02
- Registration Number
- NCT02680847
- Lead Sponsor
- Pfizer
- Brief Summary
Safety and pharmacokinetics of an abuse-deterrent, extended-release formulation of oxycodone hydrochloride with a sequestered naltrexone core in children 7-17 with moderate-severe pain.
- Detailed Description
This is a multicenter, open-label, single-arm study designed to characterize the PK and to evaluate the safety of ALO-02 in children and adolescents 7 to 17 years of age who require opioid analgesia for moderate-to-severe pain. The study consists of 4 study periods (screening, titration, maintenance, follow-up) occurring over a period of up to 9 weeks. The study will enroll approximately 140 children and adolescents with at least 100 subjects once stabilized during the titration period to complete a minimum of 2 of the 4 weeks study duration in the maintenance period to satisfy the PK endpoint. A safety follow-up visit is required at 1 week post-last dose.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 32
- Children 7-17 with moderate to severe pain requiring around the clock treatment with an opioid analgesic.
- Be an experienced opioid user, defined as any subject treated with opioid therapy, equivalent or equal to > 6 mg per day of oxycodone, for a period of 3 consecutive days immediately prior to first day of dosing.
- Columbia-Suicide Severity Rating Scale (C-SSRS) for suicidal ideation and behavior in past year.
- Hypersensitivity to morphine, naltrexone.
- A life expectancy (assessed by investigator) of less than 6 months or is no longer capable of taking medication orally.
- Undergone surgery within 3 days prior to the first day of dosing.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description ALO-02 ALO-02 One arm, open label, active
- Primary Outcome Measures
Name Time Method Average Steady-state Concentration (Css, av) of Oxycodone Visit 4 (Day 21,28,35 or 42) or Visit 5 if not collected at Visit 4 (early termination or end of study, which occurred on Day 35,42,49 or 56) in Maintenance Phase ALO-02 capsules consist of controlled-release pellets containing oxycodone hydrochloride (HCl) and naltrexone HCl. Oxycodone is a main component of this product.
Number of Participants With All-causality and Treatment-related Adverse Events (AEs) Baseline up to Day 63 An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. All-causality AEs refer to any AE occurrence which needed not necessarily have a causal relationship with the treatment or usage. Treatment-related AEs refer to AEs that have a causal relationship with the treatment or usage. The majority of AEs were of mild to moderate severity.
Number of All-causality and Treatment-related AEs, by Intensity Baseline up to Day 63 An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. All-causality AEs refer to any AE occurrence which needed not necessarily have a causal relationship with the treatment or usage. Treatment-related AEs refer to AEs that have a causal relationship with the treatment or usage. The majority of AEs were of mild to moderate severity.
Apparent Oral Clearance (CL/F) of Oxycodone Visit 4 (Day 21,28,35 or 42) or Visit 5 if not collected at Visit 4 (early termination or end of study, which occurred on Day 35,42,49 or 56) in Maintenance Phase ALO-02 capsules consist of controlled-release pellets containing oxycodone hydrochloride (HCl) and naltrexone HCl. Oxycodone is a main component of this product.
Number of Participants With All-causality and Treatment-related Serious Adverse Events (SAEs) Baseline up to Day 63 An SAE was any untoward medical occurrence at any dose that: resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. All-causality SAEs refer to any SAE occurrence which needed not necessarily have a causal relationship with the treatment or usage. Treatment-related SAEs refer to SAEs that have a causal relationship with the treatment or usage.
Number of Participants With Clinical Opiate Withdrawal Scale (COWS) Screening, Day 1, Titration Phase: Weeks 1,2,3,4; end of titration phase; Maintenance phase: Weeks 2, 4; early termination at titration phase, end of maintenance phase. The COWS contains 11 common opiate withdrawal signs or symptoms rated by the clinician.The summed score of the 11 items is used to assess a subject's level of withdrawal. A subject assessed with a COWS score\>= 13 was treated for opiate withdrawal signs and symptoms according to the investigator's medical judgment. The total COWS score ranges from 0 to 48. Higher scores indicate worse outcome. Different score ranges represent different severities of withdrawal: no withdrawal (\<5), mild (5-12), moderate (13-24), moderately severe (25-36), and severe (\>36)
- Secondary Outcome Measures
Name Time Method Apparent Volume of Distribution (Vz/F) of Oxycodone Visit 4 (Day 21,28,35 or 42) or Visit 5 if not collected at Visit 4 (early termination or end of study, which occurred on Day 35,42,49 or 56) in Maintenance Phase ALO-02 capsules consist of controlled-release pellets containing oxycodone hydrochloride (HCl) and naltrexone HCl. Oxycodone is a main component of this product.
Systemic Exposure Levels of the Metabolites of Oxycodone (Oxymorphone and Noroxycodone), Naltrexone, and 6-β-naltrexol. Visit 4 (Day 21,28,35 or 42) or Visit 5 if not collected at Visit 4 (early termination or end of study, which occurred on Day 35,42,49 or 56) in Maintenance Phase Oxymorphone and noroxycodone are major metabolites of Oxycodone and 6-β-naltrexol is the major metabolite of naltrexol.
Number of Participants With Maximum Changes in Vital Signs (Blood Pressure, Heart Rate, Respiratory Rate) Meeting Categorical Summarization Criteria Baseline up to Day 58 Following parameters were analyzed for examinations of vital signs: resting systolic and diastolic blood pressure, heart rate, and respiratory rate. In this study, there were only participants meeting the maximum decrease from baseline in systolic blood pressure (SBP) \>= 30 mmHg and diastolic blood pressure (DBP) \>=20 mmHg criteria. None of the vital sign changes were clinically significant.
Number of Participants With Laboratory (Lab) Abnormalities (Hematology and Chemistry) Baseline up to Day 77 Following parameters were analyzed for hematologic laboratory tests: hemoglobin, hematocrit, red blood cells, mean corpuscular volume, platelets, white blood cells, lymphocytes (absolute \& %), neutrophils (absolute \& %), basophils (absolute \& %), eosinophils (absolute \&%), monocytes (absolute \& %). Following parameters were analyzed for chemical laboratory tests: bilirubin,aspartate aminotransferase, alanine aminotransferase,alkaline phosphatase, protein(total), albumin,blood urea nitrogen, creatinine, cholesterol, sodium, potassium,chloride, calcium, phosphate, bicarbonate, glucose, creatine kinase. None of the lab abnormalities were clinically significant.
Trial Locations
- Locations (16)
Leo Jenkins Cancer Center Pharmacy
🇺🇸Greenville, North Carolina, United States
Children's Hospital Of Los Angeles - University Of Southern California School Of Medicine
🇺🇸Los Angeles, California, United States
University of Illinois Hospital at the Medical Center
🇺🇸Chicago, Illinois, United States
University of Illinois Hospital and Health Sciences Systems
🇺🇸Chicago, Illinois, United States
University of Illinois at Chicago Clinical Research Center
🇺🇸Chicago, Illinois, United States
Research Center For Clinical Studies-West, Inc.
🇺🇸Lancaster, California, United States
Children's Hopsital Los Angeles
🇺🇸Los Angeles, California, United States
Medical University of South Carolina, Investigational Drugs Services
🇺🇸Charleston, South Carolina, United States
Road Runner Research, Ltd
🇺🇸San Antonio, Texas, United States
Shriners Hospitals For Children Northern California
🇺🇸Sacramento, California, United States
UC Davis Health Attn: Peter Trovitch, PharmD
🇺🇸Sacramento, California, United States
University of California Davis
🇺🇸Sacramento, California, United States
East Carolina University Brody School of Medicine(ECU)
🇺🇸Greenville, North Carolina, United States
Medical University of South Carolina, SCTR Research Nexus
🇺🇸Charleston, South Carolina, United States
Medical University of South Carolina Children's Hospital
🇺🇸Charleston, South Carolina, United States
Medical University of South Carolina, Rutledge Tower, Pediatric Clinic
🇺🇸Charleston, South Carolina, United States