Trial Outcomes & Findings for Study to Compare Oxymorphone Extended-Release (Opana ER) Versus Oxycodone Controlled-Release (Oxycontin) (NCT NCT00955110)

NCT ID: NCT00955110

Last Updated: 2017-10-05

Results Overview

The High Visual Analog Scale (VAS) consisted of a horizontal line with a statement presented above the bar ("I am feeling high"). The ends of the line were marked with the descriptive anchors ("Definitely not" and "Definitely so"). Using a laptop computer, participants were instructed to click and drag the mouse to the appropriate position along the line, according to how they felt at that moment. Each scale was scored as an integer from 0 (Definitely not) to 100 (Definitely so), representing the position on the line.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 78 participants
• Primary outcome timeframe: High VAS was administered at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose.
• Results posted on: 2017-10-05

Participant Flow

The period of recruitment was from 29 May 2009 (first subject enrolled) to 01 September 2009 (last subject completed).

A double-blind crossover qualification phase (hydromorphone 8 mg vs. placebo) was followed by a washout period and then randomization to a 5-period, 10-sequence crossover treatment phase. Approximately 40 qualified subjects were to be enrolled in the treatment phase in order to ensure that at least 30 subjects completed all 5 periods of the study.

Participant milestones

Measure	All Subjects Subjects enrolled were healthy non-dependent recreational opioid users. During the Treatment Phase, subjects were randomized to 1 of 10 treatment sequences, according to two 5 × 5 Williams squares. Subjects received single oral doses of each of the following 5 treatments, in a randomized, double-blind, crossover manner (1 capsule per treatment period): Placebo, Oxymorphone ER 15 mg, Oxymorphone ER 30 mg, Oxycodone CR 30 mg, and Oxycodone CR 60 mg. All participants did not necessarily receive the 5 drug interventions in the order reported as Milestones.
Qualification Phase STARTED	78
Qualification Phase COMPLETED	54
Qualification Phase NOT COMPLETED	24
Treatment Phase STARTED	41
Treatment Phase Placebo	38
Treatment Phase Oxymorphone ER 15 mg	37
Treatment Phase Oxymorphone ER 30 mg	38
Treatment Phase Oxycodone CR 30 mg	40
Treatment Phase Oxycodone CR 60 mg	40
Treatment Phase COMPLETED	35
Treatment Phase NOT COMPLETED	6

Reasons for withdrawal

Measure	All Subjects Subjects enrolled were healthy non-dependent recreational opioid users. During the Treatment Phase, subjects were randomized to 1 of 10 treatment sequences, according to two 5 × 5 Williams squares. Subjects received single oral doses of each of the following 5 treatments, in a randomized, double-blind, crossover manner (1 capsule per treatment period): Placebo, Oxymorphone ER 15 mg, Oxymorphone ER 30 mg, Oxycodone CR 30 mg, and Oxycodone CR 60 mg. All participants did not necessarily receive the 5 drug interventions in the order reported as Milestones.
Qualification Phase Did not meet eligibility criteria	24
Treatment Phase Adverse Event	2
Treatment Phase Administrative reasons	2
Treatment Phase Non-compliance with study restrictions	1
Treatment Phase Withdrawn by physician pre-treatment	1

Baseline Characteristics

Study to Compare Oxymorphone Extended-Release (Opana ER) Versus Oxycodone Controlled-Release (Oxycontin)

Baseline characteristics by cohort

Measure	All Subjects Randomized to Treatment Phase n=41 Participants Forty one (41) qualified subjects were randomized into the treatment phase (Randomized population). Subjects were randomized to 1 of 10 treatment sequences, according to two 5 × 5 Williams squares. Subjects received single oral doses of each of the following 5 treatments, in a randomized, double-blind, crossover manner (1 capsule per treatment period): Placebo, Oxymorphone ER 15 mg, Oxymorphone ER 30 mg, Oxycodone CR 30 mg, and Oxycodone CR 60 mg.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	41 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Age, Continuous	32.4 years STANDARD_DEVIATION 9.04 • n=93 Participants
Sex: Female, Male Female	8 Participants n=93 Participants
Sex: Female, Male Male	33 Participants n=93 Participants
Region of Enrollment Canada	41 participants n=93 Participants

PRIMARY outcome

Timeframe: High VAS was administered at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose.

Population: Per Protocol population: Subjects who received all 5 treatments and who had no major protocol deviations or other circumstances that would exclude them from the analysis. The pharmacokinetic and pharmacodynamic analyses were performed using the Per Protocol population. No imputation of missing values was performed.

The High Visual Analog Scale (VAS) consisted of a horizontal line with a statement presented above the bar ("I am feeling high"). The ends of the line were marked with the descriptive anchors ("Definitely not" and "Definitely so"). Using a laptop computer, participants were instructed to click and drag the mouse to the appropriate position along the line, according to how they felt at that moment. Each scale was scored as an integer from 0 (Definitely not) to 100 (Definitely so), representing the position on the line.

Outcome measures

Measure	Placebo n=35 Participants Subjects received a single oral dose (1 capsule) of placebo.	Oxymorphone ER 15 mg n=35 Participants Subjects received a single oral dose (1 capsule) of Oxymorphone ER 15 mg.	Oxymorphone ER 30 mg n=35 Participants Subjects received a single oral dose (1 capsule) of Oxymorphone ER 30 mg.	Oxycodone CR 30 mg n=35 Participants Subjects received a single oral dose (1 capsule) of Oxycodone CR 30 mg.	Oxycodone CR 60 mg n=35 Participants Subjects received a single oral dose (1 capsule) of Oxycodone CR 60 mg.
High VAS - Emax (mm)	23.1 mm Standard Deviation 33.29 • Interval 33.29 to -16.0	30.6 mm Standard Deviation 36.17 • Interval -40.0 to -22.7	62.5 mm Standard Deviation 33.22 • Interval -19.0 to -10.6	81.4 mm Standard Deviation 23.17	93.0 mm Standard Deviation 12.94

Adverse Events

Treatment Phase Placebo

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Treatment Phase Oxymorphone ER 15 mg

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Treatment Phase Oxymorphone ER 30mg

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Treatment Phase Oxycodone CR 30mg

Serious events: 0 serious events

Other events: 35 other events

Deaths: 0 deaths

Treatment Phase Oxycodone CR 60 mg

Serious events: 0 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Treatment Phase Placebo n=38 participants at risk Identical placebo capsules using size AA Swedish orange capsules and microcrystalline cellulose.	Treatment Phase Oxymorphone ER 15 mg n=37 participants at risk Single oral dose (1 capsule) of Oxymorphone HCl ER 15 mg (OPANA® ER), overencapsulated with size AA Swedish orange capsules with microcrystalline cellulose overfill.	Treatment Phase Oxymorphone ER 30mg n=38 participants at risk Single oral dose (1 capsule) of Oxymorphone HCl ER 30 mg (OPANA® ER), overencapsulated with size AA Swedish orange capsules with microcrystalline cellulose overfill.	Treatment Phase Oxycodone CR 30mg n=40 participants at risk Single oral dose (1 capsule) of Oxycodone HCl CR 30 mg (OxyContin®), overencapsulated with size AA Swedish orange capsules with microcrystalline cellulose overfill.	Treatment Phase Oxycodone CR 60 mg n=40 participants at risk Single oral dose (1 capsule) of Oxycodone HCl CR 60 mg (OxyContin®), overencapsulated with size AA Swedish orange capsules with microcrystalline cellulose overfill.
Gastrointestinal disorders Dry mouth	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	10.0% 4/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.
Gastrointestinal disorders Nausea	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	5.4% 2/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	5.3% 2/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	15.0% 6/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	45.0% 18/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.
Gastrointestinal disorders Vomiting	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	2.5% 1/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	22.5% 9/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.
General disorders Fatigue	2.6% 1/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	2.6% 1/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	12.5% 5/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	10.0% 4/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.
General disorders Feeling hot	2.6% 1/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	2.6% 1/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	5.0% 2/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	2.5% 1/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.
General disorders Feeling of relaxation	7.9% 3/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	5.4% 2/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	7.9% 3/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	7.5% 3/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	2.5% 1/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.
Musculoskeletal and connective tissue disorders Sensation of heaviness	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	5.0% 2/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.
Nervous system disorders Disturbance in attention	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	2.5% 1/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	5.0% 2/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.
Nervous system disorders Dizziness	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	10.8% 4/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	5.3% 2/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	17.5% 7/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	20.0% 8/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.
Nervous system disorders Headache	2.6% 1/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	10.8% 4/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	7.9% 3/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	10.0% 4/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	10.0% 4/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.
Nervous system disorders Hypoaesthesia	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	2.5% 1/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	7.5% 3/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.
Nervous system disorders Sedation	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	5.4% 2/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	2.5% 1/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.
Nervous system disorders Somnolence	18.4% 7/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	21.6% 8/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	26.3% 10/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	30.0% 12/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	32.5% 13/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.
Psychiatric disorders Abnormal dreams	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	2.7% 1/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	5.0% 2/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	2.5% 1/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.
Psychiatric disorders Euphoric mood	5.3% 2/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	24.3% 9/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	52.6% 20/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	67.5% 27/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	92.5% 37/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.
Respiratory, thoracic and mediastinal disorders Nasal discomfort	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	2.7% 1/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	10.0% 4/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	20.0% 8/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	2.6% 1/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	17.5% 7/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	20.0% 8/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.
Skin and subcutaneous tissue disorders Pruritus generalised	0.00% 0/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	0.00% 0/37 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	2.6% 1/38 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	12.5% 5/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.	12.5% 5/40 • AEs were documented in the eCRF and/or source documents, whether considered treatment-related or not related, throughout the study (ie, from first dose of study drug in the qualification phase to 30 days following the last dose of study drug). AEs were any new (or increased severity of) signs, symptoms, injury, or illness. Conditions existing prior to screening were recorded as the subject's medical history; events occurring from screening until first dose of study drug in the qualification phase were recorded as baseline signs and symptoms. AEs were reported for the safety population.

Additional Information

Clinical Trial Coordinator

Endo Pharmaceuticals, Inc.

Email: clinicalsite.inquiries@endo.com

Results disclosure agreements

• Principal investigator is a sponsor employee Any analysis and/or publication of any data generated or arising from the study is not permitted without the prior written consent of Endo Pharmaceuticals Inc.
• Publication restrictions are in place

Restriction type: OTHER