Trial Outcomes & Findings for OTR Tablet 40 mg Fed-state Bioequivalence Study (NCT NCT03398330)

NCT ID: NCT03398330

Last Updated: 2019-11-15

Results Overview

The analysis was for PK parameters Cmax of analyte oxycodone. Analysis of Variance (ANOVA) with fixed effect terms for treatment, period, sequence, and subject within sequence for ratio of means (using log scale) were used to compare the test and the reference treatments.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 42 participants
• Primary outcome timeframe: up to 32 hours
• Results posted on: 2019-11-15

Participant Flow

42, from Mar2017 to Sep2017, from patient database, medical clinic, advertisement recruitment and etc.

Participant milestones

Measure	OTR 40 Mg-OXYCONTIN 40 mg the treatment sequence is OTR 40 mg dose first and then OXYCONTIN 40 mg dose in fed state	OXYCONTIN 40 Mg-OTR 40 mg the treatment sequence is OXYCONTIN 40 mg dose first and then OTR 40 mg dose in fed state
Period 1 STARTED	21	21
Period 1 COMPLETED	20	17
Period 1 NOT COMPLETED	1	4
Period 2 STARTED	20	17
Period 2 COMPLETED	19	17
Period 2 NOT COMPLETED	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

OTR Tablet 40 mg Fed-state Bioequivalence Study

Baseline characteristics by cohort

Measure	OTR 40 Mg-OXYCONTIN 40 mg n=21 Participants the treatment sequence is OTR 40 mg dose first and then OXYCONTIN 40 mg dose	OXYCONTIN 40 Mg-OTR 40 mg n=21 Participants the treatment sequence is OXYCONTIN 40 mg dose first and then OTR 40 mg dose in fed	Total n=42 Participants Total of all reporting groups
Age, Continuous	36.4 years STANDARD_DEVIATION 13.47 • n=5 Participants	38.8 years STANDARD_DEVIATION 10.12 • n=7 Participants	37.6 years STANDARD_DEVIATION 11.83 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Race/Ethnicity, Customized HAN	21 Participants n=5 Participants	21 Participants n=7 Participants	42 Participants n=5 Participants
Weight	60.80 kg STANDARD_DEVIATION 8.874 • n=5 Participants	63.40 kg STANDARD_DEVIATION 9.211 • n=7 Participants	62.10 kg STANDARD_DEVIATION 9.030 • n=5 Participants
Height	164.1 cm STANDARD_DEVIATION 8.25 • n=5 Participants	162.4 cm STANDARD_DEVIATION 8.31 • n=7 Participants	163.3 cm STANDARD_DEVIATION 8.22 • n=5 Participants
BMI	22.50 kg/m2 STANDARD_DEVIATION 2.195 • n=5 Participants	23.95 kg/m2 STANDARD_DEVIATION 2.243 • n=7 Participants	23.23 kg/m2 STANDARD_DEVIATION 2.310 • n=5 Participants

PRIMARY outcome

Timeframe: up to 32 hours

The analysis was for PK parameters Cmax of analyte oxycodone. Analysis of Variance (ANOVA) with fixed effect terms for treatment, period, sequence, and subject within sequence for ratio of means (using log scale) were used to compare the test and the reference treatments.

Outcome measures

Measure	Cmax of OTR Tablet 40 mg n=37 Participants OTR Tablet 40 mg	Cmax of OXYCONTIN Tablet 40 mg n=36 Participants OXYCONTIN Tablet 40 mg
Cmax of OTR Tablet 40 mg and OXYCONTIN Tablet 40 mg in a Fed State	86.15 ng/ml Interval 67.895 to 104.405	63.54 ng/ml Interval 50.035 to 77.045

PRIMARY outcome

Timeframe: up to 32 hours

The analysis was for PK parameters AUCt of analyte oxycodone. Analysis of Variance (ANOVA) with fixed effect terms for treatment, period, sequence, and subject within sequence for ratio of means (using log scale) were used to compare the test and the reference treatments.

Outcome measures

Measure	Cmax of OTR Tablet 40 mg n=37 Participants OTR Tablet 40 mg	Cmax of OXYCONTIN Tablet 40 mg n=36 Participants OXYCONTIN Tablet 40 mg
AUCt of OTR Tablet 40 mg and OXYCONTIN Tablet 40 mg in a Fed State	641.3017 ng*h/ml Interval 517.97802 to 764.62538	646.2133 ng*h/ml Interval 514.12207 to 778.30453

PRIMARY outcome

Timeframe: up to 32 hours

The analysis was for PK parameters AUCINF for analyte oxycodone. Analysis of Variance (ANOVA) with fixed effect terms for treatment, period, sequence, and subject within sequence for ratio of means (using log scale) was used to compare the test and the reference treatments.

Outcome measures

Measure	Cmax of OTR Tablet 40 mg n=37 Participants OTR Tablet 40 mg	Cmax of OXYCONTIN Tablet 40 mg n=36 Participants OXYCONTIN Tablet 40 mg
AUCINF of OTR Tablet 40 mg and OXYCONTIN Tablet 40 mg in a Fed State	648.2546 ng*h/ml Interval 521.43808 to 775.07112	664.0493 ng*h/ml Interval 521.26837 to 806.8302

SECONDARY outcome

Timeframe: up to 35 days

An overall summary of the number and percentage of Adverse Events will be provided for each treatment groups to assess the safety of OTR tablet 40 mg and OXYCONTIN® tablet 40 mg.

Outcome measures

Measure	Cmax of OTR Tablet 40 mg n=37 Participants OTR Tablet 40 mg	Cmax of OXYCONTIN Tablet 40 mg n=40 Participants OXYCONTIN Tablet 40 mg
Adverse Events of OTR Tablet 40 mg and OXYCONTIN Tablet 40 mg, When Given to Chinese Subjects With Chronic Pain in a Fed State Number of TEAEs (#)	29 TEAEs	35 TEAEs
Adverse Events of OTR Tablet 40 mg and OXYCONTIN Tablet 40 mg, When Given to Chinese Subjects With Chronic Pain in a Fed State Number of AEs (#)	29 TEAEs	37 TEAEs
Adverse Events of OTR Tablet 40 mg and OXYCONTIN Tablet 40 mg, When Given to Chinese Subjects With Chronic Pain in a Fed State Number of relateda TEAEs	20 TEAEs	30 TEAEs

SECONDARY outcome

Timeframe: up to 35 days

Clinical laboratory data to be summarised includes haematology, blood chemistry, and urinalysis.Each parameter will be assigned an LNH classification according to whether the value is lower than (L), within (N) or higher than (H) the reference range for that parameter. Results will be summarised using shift tables to evaluate categorical changes from baseline to end of study with respect to reference range values (lower than, within, and higher than).

Outcome measures

Measure	Cmax of OTR Tablet 40 mg n=37 Participants OTR Tablet 40 mg	Cmax of OXYCONTIN Tablet 40 mg n=40 Participants OXYCONTIN Tablet 40 mg
Number of Lab Tests With Clinical Significance	5 Lab tests with clinical significance	11 Lab tests with clinical significance

SECONDARY outcome

Timeframe: up to 35 days

Vital sign parameters to be summarised include systolic blood pressure, diastolic blood pressure, pulse rate, respiration rate, and axillary temperature.Vital sign results for each parameter will be assigned an LNH classification according to whether the value is lower than (L), within (N), or higher than (H) the reference range for that parameter. Vital sign results will be summarised using shift tables to evaluate categorical changes from baseline to end of study with respect to reference range values (lower than, within, and higher than).

Outcome measures

Measure	Cmax of OTR Tablet 40 mg n=37 Participants OTR Tablet 40 mg	Cmax of OXYCONTIN Tablet 40 mg n=40 Participants OXYCONTIN Tablet 40 mg
Number of AEs Related to Vital Signs	0 AEs of vital signs related	1 AEs of vital signs related

SECONDARY outcome

Timeframe: up to 35 days

Summarized table of 12-lead ECG is presented. ECG was measured at Screening and 4 days after IMP dosing in Period 2.

Outcome measures

Measure	Cmax of OTR Tablet 40 mg n=37 Participants OTR Tablet 40 mg	Cmax of OXYCONTIN Tablet 40 mg n=40 Participants OXYCONTIN Tablet 40 mg
Number of AEs Related to ECGs	0 AEs of ECG related	1 AEs of ECG related

SECONDARY outcome

Timeframe: up to 35 days

Physical examination were measured at Screening, 1 day before IMP dosing and 4 days after IMP dosing in each period.

Outcome measures

Measure	Cmax of OTR Tablet 40 mg n=37 Participants OTR Tablet 40 mg	Cmax of OXYCONTIN Tablet 40 mg n=40 Participants OXYCONTIN Tablet 40 mg
Number of AEs Related to Physical Examination	1 AEs related to Physical examination	1 AEs related to Physical examination

Adverse Events

OTR 40mg

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

OXYCONTIN® 40mg

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	OTR 40mg n=37 participants at risk Oxycodone Tamper Resistant (OTR) Tablet 40 mg Oxycodone Tamper Resistant: Orally taking Oxycodone Tamper Resistant 40mg in fed state	OXYCONTIN® 40mg n=40 participants at risk OXYCONTIN® Tablet 40 mg OxyContin®: Orally taking OXYCONTIN® 40mg in fed state
Injury, poisoning and procedural complications Drug-induced liver injury	2.7% 1/37 • Number of events 1 • Events will be recorded from the point at which the ICF is signed until 7±1 days after last oxycodone dose in the case of completion/discontinuation from the study. This includes new AEs that are reported within 7±1 days after last oxycodone dosing after the subject's completion/discontinuation visit. same with clinicaltrials.gov Definitions.	0.00% 0/40 • Events will be recorded from the point at which the ICF is signed until 7±1 days after last oxycodone dose in the case of completion/discontinuation from the study. This includes new AEs that are reported within 7±1 days after last oxycodone dosing after the subject's completion/discontinuation visit. same with clinicaltrials.gov Definitions.

Other adverse events

Measure	OTR 40mg n=37 participants at risk Oxycodone Tamper Resistant (OTR) Tablet 40 mg Oxycodone Tamper Resistant: Orally taking Oxycodone Tamper Resistant 40mg in fed state	OXYCONTIN® 40mg n=40 participants at risk OXYCONTIN® Tablet 40 mg OxyContin®: Orally taking OXYCONTIN® 40mg in fed state
Gastrointestinal disorders Nausea	10.8% 4/37 • Number of events 4 • Events will be recorded from the point at which the ICF is signed until 7±1 days after last oxycodone dose in the case of completion/discontinuation from the study. This includes new AEs that are reported within 7±1 days after last oxycodone dosing after the subject's completion/discontinuation visit. same with clinicaltrials.gov Definitions.	10.0% 4/40 • Number of events 4 • Events will be recorded from the point at which the ICF is signed until 7±1 days after last oxycodone dose in the case of completion/discontinuation from the study. This includes new AEs that are reported within 7±1 days after last oxycodone dosing after the subject's completion/discontinuation visit. same with clinicaltrials.gov Definitions.
Gastrointestinal disorders Vomit	0.00% 0/37 • Events will be recorded from the point at which the ICF is signed until 7±1 days after last oxycodone dose in the case of completion/discontinuation from the study. This includes new AEs that are reported within 7±1 days after last oxycodone dosing after the subject's completion/discontinuation visit. same with clinicaltrials.gov Definitions.	10.0% 4/40 • Number of events 8 • Events will be recorded from the point at which the ICF is signed until 7±1 days after last oxycodone dose in the case of completion/discontinuation from the study. This includes new AEs that are reported within 7±1 days after last oxycodone dosing after the subject's completion/discontinuation visit. same with clinicaltrials.gov Definitions.
Endocrine disorders Blood triglycerides increased	2.7% 1/37 • Number of events 1 • Events will be recorded from the point at which the ICF is signed until 7±1 days after last oxycodone dose in the case of completion/discontinuation from the study. This includes new AEs that are reported within 7±1 days after last oxycodone dosing after the subject's completion/discontinuation visit. same with clinicaltrials.gov Definitions.	12.5% 5/40 • Number of events 5 • Events will be recorded from the point at which the ICF is signed until 7±1 days after last oxycodone dose in the case of completion/discontinuation from the study. This includes new AEs that are reported within 7±1 days after last oxycodone dosing after the subject's completion/discontinuation visit. same with clinicaltrials.gov Definitions.

Additional Information

Rongna. A

Mundipharma(China) Pharmaceutical. Co. Ltd

Phone: 86 10 65636885

Email: rongna.a@mundipharma.com.cn

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place