Clinical trial NCT03398278: OTR Tablet 40 mg Fasted-state Bioequivalence Study
Official title: An Open-label, Single Dose, Randomised, Cross-over Study to Determine the Fasted State Pharmacokinetics of Oxycodone From Oxycodone Tamper Resistant (OTR) Tablet 40 mg and OXYCONTIN® Tablet 40 mg in Chinese Subjects With Chronic Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Pain
Lead sponsor: Mundipharma (China) Pharmaceutical Co. Ltd
Sponsor class: INDUSTRY
First posted: 2018-01-12
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: This is an open-label, single dose, randomised, cross-over study to confirm the bioequivalence (BE) of OTR tablet 40 mg and OXYCONTIN tablet 40 mg in a fasted state in Chinese subjects with chronic pain

Detailed description: In this BE study, subjects with histories of chronic pain are chosen as the target population.

Inclusion/exclusion criteria are strictly defined to reduce the potential variation of the PK data.

Single dose design is chosen per Food and Drug Administration (FDA)/WHO guideline on bioavailability (BA)/BE studies for modified-release products.

As a general rule, cross-over design is applied in the study to decrease the inter-individual variations between the two cohorts. A washout period lasting for at least 7 half-lives of the investigational medicine is needed to eliminate the drug residual from the previous period7. The elimination half-life of oxycodone from OTR is 4.5 hours, and a 6-day washout period is sufficient to achieve the aim.

Eligibility criteria: Inclusion Criteria:

1. Chinese male or female subjects with histories of chronic pain regardless of the aetiology, aged 18-55 years both inclusive
2. The average pain over the last 24 hours should be scored \< 4 assessed with Numeric Rating Scales (NRS), when not receiving analgesics. The pain condition has been kept stable at least in the past 7 days prior to entering into the screening and is expected to be stable during the study duration
3. Body weight ≥45 kg and a body mass index (BMI) ≥18 and ≤28 kg/m2
4. Karnofsky score of Performance Status ≥70
5. Willing to take all the food supplied while the subject is in the study unit
6. Be able to read, understand, and sign written Informed Consent Form (ICF) prior to study participation and be willing to follow the protocol requirements
7. Willing to use adequate and highly effective methods of contraception throughout the study. A highly effective method of birth control is defined as one which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as sterilisation, implants, injectables, some Intrauterine Device (IUD), sexual abstinence, or vasectomised partner
8. Female subjects, including those up to less than one year post-menopausal, must have a negative serum pregnancy test and be non-lactating

Exclusion Criteria:

1. Subjects who are currently taking opioids or have used opioids in the past 14 days prior to receiving the study drug
2. Have hypersensitivity history to any opioids, naltrexone, naloxone, or related compounds or any contraindications as detailed in the OTR and OXYCONTIN tablet Summary of Product Characteristics
3. Histories of or any current conditions that might interfere with drug absorption, distribution, metabolism, or excretion
4. Subjects who are likely to have paralytic ileus or acute abdomen or to require an operation on abdominal regions
5. Subjects with biliary tract diseases, pancreatitis, prostatic hypertrophy, or corticoadrenal insufficiency
6. Subjects with respiratory depression, corpulmonale, or chronic bronchial asthma
7. Any history of seizures or symptomatic head trauma
8. Subjects with abnormal liver function (values exceeding the upper limit of normal (ULN) for alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin during the Screening Phase) or abnormal renal function (values exceeding the ULN for serum creatinine during the Screening Phase). Note: if the values of ALT, AST or total bilirubin are between 1 to 1.2 times of ULN and confirmed not clinically significant by the Investigators, the subject may be recruited after getting the approval from Sponsor.
9. Any other significant illness other than the primary disease of chronic pain during the 4 weeks preceding the entry into this study
10. Subjects who are unable to stop taking monoamine oxidase inhibitors during this trial period or time lapses less than 2 weeks since drug withdrawal prior to the study drug administration
11. Subjects who are currently taking tricyclic antidepressants or have used tricyclic antidepressants within 4 weeks prior to the study drug administration
12. Subjects who have used any medicinal product which inhibits Cytochrome P450 3A4 (CYP3A4) (e.g. troleandomycin, ketoconazole, gestodene, etc.) or induces CYP3A4 (e.g. glucocorticoids, barbiturates, rifampicin, etc.) within 4 weeks prior to the study drug administration
13. Subjects who have used any medicinal product which inhibits Cytochrome P450 2D6 (CYP2D6) (e.g. fluoxetine, quinidine, ritonavir, etc.) or induces CYP2D6 (e.g. dexamethasone, rifampicin, glutethimide, etc.) within 4 weeks prior to the study drug administration
14. Histories of smoking (being a smoker or an occasional smoker) within 45 days prior to the study drug administration and refusal to abstain from smoking during the study. According to World Health Organization (WHO), a smoker is defined as having smoked at least 1 cigarette per day continuously for more than 6 months and an occasional smoker is defined as having smoked for more than 4 times per week and less than 1 cigarette per day continuously for more than 6 months.
15. Subjects with histories of alcoholism or drug abuse. Alcoholism is defined as regular alcohol consumption exceeding 14 drinks/week (1 drink = 150 mL of wine or 360 mL of beer or 45 mL of hard liquor)
16. Consumption of alcoholic beverages within 48 hours before study drug administration, and refusal to abstain from alcohol for at least 48 hours after study drug administration
17. Refusal to abstain from food for 10 hours preceding and 4 hours following administration of the study drug and to abstain from caffeine or xanthine entirely during each confinement
18. Positive Hepatitis B Surface Antigen (HBsAg), anti-Hepatitis C Virus (HCV), anti-Human Immunodeficiency Virus (HIV), or syphilis antibody test result
19. Urine screening before study is positive for opioids, barbiturates, amphetamines, cocaine metabolites, methadone, benzodiazepines, phencyclidine, methamphetamine, or cannabinoids. Or alcohol breath test is positive
20. Any history of frequent nausea or emesis regardless of aetiology
21. Blood or blood products donated within 30 days prior to administration of the study drugs or anytime during the study, except as required by this protocol
22. Subjects who participated in a clinical research study within 30 days of study entry

Primary outcomes:
measure: Cmax of OTR Tablet 40 mg and OXYCONTIN Tablet 40 mg in a Fasted State
timeFrame: up to 32 hours
measure: AUCt of OTR Tablet 40 mg and OXYCONTIN Tablet 40 mg in a Fasted State
timeFrame: up to 32 hours
measure: AUCINF of OTR Tablet 40 mg and OXYCONTIN Tablet 40 mg in a Fasted State
timeFrame: up to 32 hours
Secondary outcomes:
measure: Adverse Event of OTR Tablet 40 mg and OXYCONTIN Tablet 40 mg, When Given to Chinese Subjects With Chronic Pain in a Fasted State
timeFrame: up to 35 days
measure: Number of Lab Tests With Clinical Significance
timeFrame: up to 35 days
measure: Number of AEs Related to Vital Sign
timeFrame: up to 35 days
measure: Number of AEs Related to ECGs
timeFrame: up to 35 days
measure: Number of AEs Related to Physical Examination
timeFrame: up to 35 days
Other outcomes:
Locations:
city: Chengdu
country: China
facility: West Hospital, Sichuan University
state: Sichuan
Study officials:
affiliation: West Hospital, Sichuan University
name: ZHU LUO, PhD
role: PRINCIPAL_INVESTIGATOR
References: