Safety and Pharmacokinetic Study of ALO-02 in Children Ages 7-17 With Pain

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open-label Study To Evaluate The Pharmacokinetics And Safety Of Alo-02 (Oxycodone Hydrochloride And Naltrexone Hydrochloride) Extended-release Capsules In Children And Adolescents 7-17 Years Of Age Who Require Opioid Analgesia

Conditions
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Moderate-severe Pain

Intervention / Treatment
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* Drug: ALO-02


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALO-02<br>One arm, open label, active | Drug: ALO-02<br>* Oral/Capsule, twice per day dosing; Treatment duration consists of a 1 to 4 week Conversion/Titration Phase leading to a 2 to 4 week Maintenance Treatment duration.<br>* Other names: oxycodone hydrochloride/naltrexone hydrochloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Steady-state Concentration (Css, av) of Oxycodone | ALO-02 capsules consist of controlled-release pellets containing oxycodone hydrochloride (HCl) and naltrexone HCl. Oxycodone is a main component of this product. | 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 | 
| Apparent Oral Clearance (CL/F) of Oxycodone | ALO-02 capsules consist of controlled-release pellets containing oxycodone hydrochloride (HCl) and naltrexone HCl. Oxycodone is a main component of this product. | 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 | 
| Number of Participants With All-causality and Treatment-related Adverse Events (AEs) | 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. | Baseline up to Day 63 | 
| Number of All-causality and Treatment-related AEs, by Intensity | 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. | Baseline up to Day 63 | 
| Number of Participants With All-causality and Treatment-related Serious Adverse Events (SAEs) | 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. | Baseline up to Day 63 | 
| Number of Participants With Clinical Opiate Withdrawal Scale (COWS) | 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) | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apparent Volume of Distribution (Vz/F) of Oxycodone | ALO-02 capsules consist of controlled-release pellets containing oxycodone hydrochloride (HCl) and naltrexone HCl. Oxycodone is a main component of this product. | 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 | 
| Systemic Exposure Levels of the Metabolites of Oxycodone (Oxymorphone and Noroxycodone), Naltrexone, and 6-β-naltrexol. | Oxymorphone and noroxycodone are major metabolites of Oxycodone and 6-β-naltrexol is the major metabolite of 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 | 
| Number of Participants With Maximum Changes in Vital Signs (Blood Pressure, Heart Rate, Respiratory Rate) Meeting Categorical Summarization Criteria | 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. | Baseline up to Day 58 | 
| Number of Participants With Laboratory (Lab) Abnormalities (Hematology and Chemistry) | 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. | Baseline up to Day 77 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric, pain indication, controlled release oxycodone