Trial Outcomes & Findings for A118G SNP and OPRM1 Gene Opioid-Mediated Effects in Humans (NCT NCT02360371)

NCT ID: NCT02360371

Last Updated: 2025-02-27

Results Overview

Peak visual analog rating scale values of HIGH (rated on 0-100 scale with higher scores indicating higher feeling of being HIGH) collected at 30 minute intervals post-drug administration for 6 hours.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 100 participants
• Primary outcome timeframe: 30 minutes after study drug administration
• Results posted on: 2025-02-27

Participant Flow

100 participants were recruited from the community for participation. Analyses were based upon OPRM1 rs-1799971 allele status (A, G), which was available for 97 participants. All participants completed the same 4 study arms.

Participant milestones

Measure	A118G (rs1799971-G) This is a within-subject study wherein the same participants moved from one treatment arm to the next and results were analyzed posthoc as a function of genotype.	A118A (rs1799971-A) This is a within-subject study wherein the same participants moved from one treatment arm to the next and results were analyzed posthoc as a function of genotype.
Overall Study STARTED	13	84
Overall Study Placebo (Oral)	13	69
Overall Study Hydromorphone (Oral) 2mg	13	69
Overall Study Hydromorphone (Oral) 4mg	13	69
Overall Study Hydromorphone (Oral) 8mg	13	69
Overall Study COMPLETED	13	69
Overall Study NOT COMPLETED	0	15

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A118G SNP and OPRM1 Gene Opioid-Mediated Effects in Humans

Baseline characteristics by cohort

Measure	A118G (rs1799971-G) n=13 Participants This is a within-subject study wherein the same 100 participants moved from one treatment arm to the next.	A118A (rs1799971-A) n=84 Participants This is a within-subject study wherein the same 100 participants moved from one treatment arm to the next.	Total n=97 Participants Total of all reporting groups
Age, Continuous	37.6 years STANDARD_DEVIATION 10.0 • n=5 Participants	33.3 years STANDARD_DEVIATION 8.9 • n=7 Participants	33.9 years STANDARD_DEVIATION 9.1 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	45 Participants n=7 Participants	49 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	39 Participants n=7 Participants	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	79 Participants n=7 Participants	89 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	43 Participants n=7 Participants	45 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	28 Participants n=7 Participants	37 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	13 participants n=5 Participants	84 participants n=7 Participants	97 participants n=5 Participants

PRIMARY outcome

Timeframe: 30 minutes after study drug administration

Peak visual analog rating scale values of HIGH (rated on 0-100 scale with higher scores indicating higher feeling of being HIGH) collected at 30 minute intervals post-drug administration for 6 hours.

Outcome measures

Measure	A118G (rs1799971-G) n=13 Participants This is a within-subject study wherein the same 100 participants moved from one treatment arm to the next.	A118A (rs1799971-A) n=84 Participants This is a within-subject study wherein the same 100 participants moved from one treatment arm to the next.
Self-report Visual Analog Ratings of HIGH Placebo (oral)	7.2 score on a scale Standard Deviation 13.2	6.6 score on a scale Standard Deviation 16.3
Self-report Visual Analog Ratings of HIGH Hydromorphone (oral) 2mg	4.5 score on a scale Standard Deviation 5.9	5.6 score on a scale Standard Deviation 15.4
Self-report Visual Analog Ratings of HIGH Hydromorphone (oral) 4mg	12.5 score on a scale Standard Deviation 19.8	18.4 score on a scale Standard Deviation 26.4
Self-report Visual Analog Ratings of HIGH Hydromorphone (oral) 8mg	25.5 score on a scale Standard Deviation 29.7	22.5 score on a scale Standard Deviation 27.2

PRIMARY outcome

Timeframe: 30 minutes after study drug administration

Peak visual analog rating scale values of DRUG EFFECT (rated on 0-100 scale with higher scores indicating higher drug effect) collected at 30 minute intervals post-drug administration for 6 hours.

Outcome measures

Measure	A118G (rs1799971-G) n=13 Participants This is a within-subject study wherein the same 100 participants moved from one treatment arm to the next.	A118A (rs1799971-A) n=84 Participants This is a within-subject study wherein the same 100 participants moved from one treatment arm to the next.
Self-report Visual Analog Ratings of DRUG EFFECT Hydromorphone (oral) 8mg	39.2 score on a scale Standard Deviation 37.3	39.5 score on a scale Standard Deviation 32.1
Self-report Visual Analog Ratings of DRUG EFFECT Placebo (oral)	13.3 score on a scale Standard Deviation 21.3	11.1 score on a scale Standard Deviation 20.0
Self-report Visual Analog Ratings of DRUG EFFECT Hydromorphone (oral) 2mg	10.8 score on a scale Standard Deviation 16.5	11.0 score on a scale Standard Deviation 20.7
Self-report Visual Analog Ratings of DRUG EFFECT Hydromorphone (oral) 4mg	23.6 score on a scale Standard Deviation 27.0	31.9 score on a scale Standard Deviation 29.9

Adverse Events

Placebo (Oral)

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Hydromorphone (Oral) 2mg

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Hydromorphone (Oral) 4mg

Serious events: 0 serious events

Other events: 65 other events

Deaths: 0 deaths

Hydromorphone (Oral) 8mg

Serious events: 0 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo (Oral) n=82 participants at risk Within-subject double-blind, administration of placebo oral capsule. Order of dose randomized session days 3-5.	Hydromorphone (Oral) 2mg n=82 participants at risk Within-subject double-blind, administration of hydromorphone via oral capsule. Order of dose randomized session days 3-5.	Hydromorphone (Oral) 4mg n=97 participants at risk Hydromorphone oral capsule administered in double-blind manner on Day 2 as first study drug administration. Hydromorphone 4mg dosing day was set for safety purposes and non-randomized.	Hydromorphone (Oral) 8mg n=82 participants at risk Within-subject double-blind, administration of hydromorphone via oral capsule. Order of dose randomized session days 3-5.
General disorders Headache	6.1% 5/82 • Number of events 5 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	9.8% 8/82 • Number of events 8 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	6.2% 6/97 • Number of events 6 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	7.3% 6/82 • Number of events 7 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.
Gastrointestinal disorders Vomiting	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	14.4% 14/97 • Number of events 16 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	8.5% 7/82 • Number of events 8 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.
General disorders Dry Mouth (Xerostomia)	1.2% 1/82 • Number of events 1 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	5.2% 5/97 • Number of events 6 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	7.3% 6/82 • Number of events 6 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.
Nervous system disorders Dizziness	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	8.2% 8/97 • Number of events 11 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	11.0% 9/82 • Number of events 10 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.
Nervous system disorders Drowsiness	12.2% 10/82 • Number of events 17 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	12.2% 10/82 • Number of events 13 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	32.0% 31/97 • Number of events 48 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	24.4% 20/82 • Number of events 35 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.
Nervous system disorders Euphoria/High	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	2.1% 2/97 • Number of events 2 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	3.7% 3/82 • Number of events 3 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.
Nervous system disorders Fatigue	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	0.00% 0/97 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	3.7% 3/82 • Number of events 6 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.
Nervous system disorders Impaired, Groggy	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	4.1% 4/97 • Number of events 4 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	4.9% 4/82 • Number of events 4 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.
Nervous system disorders Lethargy	2.4% 2/82 • Number of events 4 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	1.2% 1/82 • Number of events 1 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	9.3% 9/97 • Number of events 10 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	1.2% 1/82 • Number of events 2 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.
Nervous system disorders Light Headedness	1.2% 1/82 • Number of events 1 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	1.2% 1/82 • Number of events 1 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	10.3% 10/97 • Number of events 12 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	8.5% 7/82 • Number of events 7 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.
Nervous system disorders Shaky	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	3.1% 3/97 • Number of events 4 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	2.4% 2/82 • Number of events 3 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.
Nervous system disorders Sleepiness	1.2% 1/82 • Number of events 1 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	2.4% 2/82 • Number of events 2 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	8.2% 8/97 • Number of events 9 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	4.9% 4/82 • Number of events 4 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.
Nervous system disorders Sluggish	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	1.0% 1/97 • Number of events 1 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	6.1% 5/82 • Number of events 5 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.
Nervous system disorders Pruritus (Itching)	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	2.4% 2/82 • Number of events 2 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	4.1% 4/97 • Number of events 5 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	9.8% 8/82 • Number of events 10 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.
Nervous system disorders Hot Flashes	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	0.00% 0/82 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	3.1% 3/97 • Number of events 3 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	7.3% 6/82 • Number of events 7 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.
Gastrointestinal disorders Nausea	3.7% 3/82 • Number of events 3 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	6.1% 5/82 • Number of events 5 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	29.9% 29/97 • Number of events 39 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.	22.0% 18/82 • Number of events 29 • Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported. AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.

Additional Information

Dr. Kelly Dunn, Ph.D., MBA

Johns Hopkins University School of Medicine

Phone: 410-550-2254

Email: kdunn9@jhmi.edu

Results disclosure agreements

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