Trial Outcomes & Findings for Pharmacokinetics (PK) and Safety Study of XARTEMIS® XR in Postsurgical Adolescent Subjects With Moderate to Severe Acute Pain (NCT NCT02508935)

NCT ID: NCT02508935

Last Updated: 2020-01-22

Results Overview

The time to reach steady state in participants who received all 5 doses

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 23 participants
• Primary outcome timeframe: within 60 hours
• Results posted on: 2020-01-22

Participant Flow

The study was conducted from November 20, 2015 to April 26, 2017 and enrolled participants from the United States.

Participant milestones

Measure	XARTEMIS XR XARTEMIS XR is a combination of oxycodone and acetaminophen administered to postsurgical adolescent participants with moderate to severe acute pain.
Overall Study STARTED	23
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	23

Reasons for withdrawal

Measure	XARTEMIS XR XARTEMIS XR is a combination of oxycodone and acetaminophen administered to postsurgical adolescent participants with moderate to severe acute pain.
Overall Study Withdrawal by Subject	1
Overall Study Withdrawal by Caregiver	8
Overall Study Pain Score <4	1
Overall Study Emesis	3
Overall Study Adverse Event	3
Overall Study Protocol Violation	1
Overall Study Physician Decision	1
Overall Study Trial terminated by sponsor	5

Baseline Characteristics

Pharmacokinetics (PK) and Safety Study of XARTEMIS® XR in Postsurgical Adolescent Subjects With Moderate to Severe Acute Pain

Baseline characteristics by cohort

Measure	XARTEMIS XR n=23 Participants XARTEMIS XR is a combination of oxycodone and acetaminophen administered to postsurgical adolescent participants with moderate to severe acute pain.
Age, Continuous	14.7 years STANDARD_DEVIATION 1.39 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: within 60 hours

Population: Steady-state pharmacokinetic (PK) parameters were to be determined for those participants administered all 5 doses. However, no participant received all 5 doses; therefore, steady state PK parameters were not derived.

The time to reach steady state in participants who received all 5 doses

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: within approximately 12 hours (12.08 hours)

Population: PK population

Elimination constant estimates required for the calculation of the planned AUC0-12 hours were not available. AUClast therefore provided the best available measure of exposure, effectively representing AUC0-12 hours for both moieties. While considered the best available measure, it also remains inaccurate because of the extended-release formulation and the lack of data beyond the 12.08-hour time point.

Outcome measures

Measure	XARTEMIS XR n=18 Participants All participants received XARTEMIS XR XARTEMIS XR: XARTEMIS XR (7.5 mg oxycodone hydrochloride and 325 mg acetaminophen) Extended-Release Tablets	Acetaminophen n=18 Participants Pharmacokinetics of acetaminophen were collected for 12 hours after dosing of XARTEMIS XR on Study Day 1
Area Under the Concentration-time Curve (AUC) From Time Zero (AUC0) to the Time of the Last Quantifiable Plasma Sample (AUClast)	76.8 ng*hr/mL Interval 25.85 to 173.59	20571.4 ng*hr/mL Interval 10195.17 to 33714.5

PRIMARY outcome

Timeframe: within approximately 12 hours (12.08 hours)

Population: PK population.

The highest concentration of study drug within 12 hours.

Outcome measures

Measure	XARTEMIS XR n=18 Participants All participants received XARTEMIS XR XARTEMIS XR: XARTEMIS XR (7.5 mg oxycodone hydrochloride and 325 mg acetaminophen) Extended-Release Tablets	Acetaminophen n=18 Participants Pharmacokinetics of acetaminophen were collected for 12 hours after dosing of XARTEMIS XR on Study Day 1
Maximum Observed Plasma Concentration (Cmax)	12.8 ng/mL Standard Deviation 4.6	2886.1 ng/mL Standard Deviation 881.68

PRIMARY outcome

Timeframe: within approximately 12 hours (12.08 hours)

Population: PK population with BLQ values set to missing

PK parameters are determined after a single administration of study drug on Day 1. Plasma concentrations that are below the level of quantification (BLQ) are set to 0 before Tmax, with the exception that a BLQ value occurring between measurable concentrations is set to missing. BLQ values that occur after Tmax are set to missing.

Outcome measures

Measure	XARTEMIS XR n=10 Participants All participants received XARTEMIS XR XARTEMIS XR: XARTEMIS XR (7.5 mg oxycodone hydrochloride and 325 mg acetaminophen) Extended-Release Tablets	Acetaminophen n=16 Participants Pharmacokinetics of acetaminophen were collected for 12 hours after dosing of XARTEMIS XR on Study Day 1
Apparent Plasma Terminal Drug Elimination Half-life (T1/2)	0.52 hours Interval 0.0 to 2.83	0.00 hours Interval 0.0 to 0.97

PRIMARY outcome

Timeframe: within approximately 12 hours (12.08 hours)

Population: PK population.

The time at which the maximum plasma concentration (Cmax) is reached.

Outcome measures

Measure	XARTEMIS XR n=18 Participants All participants received XARTEMIS XR XARTEMIS XR: XARTEMIS XR (7.5 mg oxycodone hydrochloride and 325 mg acetaminophen) Extended-Release Tablets	Acetaminophen n=18 Participants Pharmacokinetics of acetaminophen were collected for 12 hours after dosing of XARTEMIS XR on Study Day 1
Time of Maximum Observed Plasma Concentration (Tmax)	7.9 hour Interval 3.92 to 12.08	4.03 hour Interval 2.07 to 12.08

Adverse Events

XARTEMIS XR

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	XARTEMIS XR n=23 participants at risk XARTEMIS XR is a combination of oxycodone and acetaminophen administered to postsurgical adolescent participants with moderate to severe acute pain.
Respiratory, thoracic and mediastinal disorders Severe pneumothorax	4.3% 1/23 • Up to 17 months. A treatment-emergent adverse event (TEAE) is defined as an evat that emerges during treatment having been absent pre-treatment or worsens relative to the pre-treatment state. Any TEAE determined as possibly related or related to the study drug is considered a treatment-related TEAE. All serious adverse events are reported, as well as all treatment-related TEAEs.
Gastrointestinal disorders Moderate Constipation	4.3% 1/23 • Up to 17 months. A treatment-emergent adverse event (TEAE) is defined as an evat that emerges during treatment having been absent pre-treatment or worsens relative to the pre-treatment state. Any TEAE determined as possibly related or related to the study drug is considered a treatment-related TEAE. All serious adverse events are reported, as well as all treatment-related TEAEs.
Nervous system disorders Severe delirium	4.3% 1/23 • Up to 17 months. A treatment-emergent adverse event (TEAE) is defined as an evat that emerges during treatment having been absent pre-treatment or worsens relative to the pre-treatment state. Any TEAE determined as possibly related or related to the study drug is considered a treatment-related TEAE. All serious adverse events are reported, as well as all treatment-related TEAEs.

Other adverse events

Measure	XARTEMIS XR n=23 participants at risk XARTEMIS XR is a combination of oxycodone and acetaminophen administered to postsurgical adolescent participants with moderate to severe acute pain.
Gastrointestinal disorders Constipation	13.0% 3/23 • Up to 17 months. A treatment-emergent adverse event (TEAE) is defined as an evat that emerges during treatment having been absent pre-treatment or worsens relative to the pre-treatment state. Any TEAE determined as possibly related or related to the study drug is considered a treatment-related TEAE. All serious adverse events are reported, as well as all treatment-related TEAEs.
Skin and subcutaneous tissue disorders Pruritis	8.7% 2/23 • Up to 17 months. A treatment-emergent adverse event (TEAE) is defined as an evat that emerges during treatment having been absent pre-treatment or worsens relative to the pre-treatment state. Any TEAE determined as possibly related or related to the study drug is considered a treatment-related TEAE. All serious adverse events are reported, as well as all treatment-related TEAEs.
General disorders Asthenia	8.7% 2/23 • Up to 17 months. A treatment-emergent adverse event (TEAE) is defined as an evat that emerges during treatment having been absent pre-treatment or worsens relative to the pre-treatment state. Any TEAE determined as possibly related or related to the study drug is considered a treatment-related TEAE. All serious adverse events are reported, as well as all treatment-related TEAEs.

Additional Information

Medical Information Call Center

Mallinckrodt Pharmaceuticals

Phone: 800-556-3314

Email: clinicaltrials@mnk.com

Results disclosure agreements

• Principal investigator is a sponsor employee Investigators will be part of the primary publication. Each investigator may publish on the data from subjects enrolled at their site after the initial publication has been submitted.
• Publication restrictions are in place

Restriction type: OTHER