Trial Outcomes & Findings for The Discriminative Effects of Tramadol in Humans (NCT NCT00499746)

Results Overview

The acquisition of discrimination was to test whether volunteers could identify each training drug condition by the correct letter code. Results are the percentage of correct responses with a range of 0% to 100%.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

20 participants

Primary outcome timeframe

1 day

Results posted on

2017-10-17

Participant Flow

Participant milestones

Participant milestones
Measure	All Participants Participant flow is reported in single group due to the number of randomized sequences. In Phase 1 and Phase 2, each participant received two exposures of each training drug in randomize order (placebo, Hydromorphone 8 mg, Methylphenidate 60 mg). In Phase 3, each participant received randomized exposure to placebo, Hydromorphone (4 and 8 mg), Methylphenidate (30 and 60 mg), tramadol (50, 100, 200, and 400 mg).
Phase 1(6-9 One Day Sessions) STARTED	20
Phase 1(6-9 One Day Sessions) COMPLETED	8
Phase 1(6-9 One Day Sessions) NOT COMPLETED	12
Phase 2 (6-9 One Day Sessions) STARTED	8
Phase 2 (6-9 One Day Sessions) COMPLETED	8
Phase 2 (6-9 One Day Sessions) NOT COMPLETED	0
Phase 3 (9-14 One Day Sessions) STARTED	8
Phase 3 (9-14 One Day Sessions) COMPLETED	8
Phase 3 (9-14 One Day Sessions) NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	All Participants Participant flow is reported in single group due to the number of randomized sequences. In Phase 1 and Phase 2, each participant received two exposures of each training drug in randomize order (placebo, Hydromorphone 8 mg, Methylphenidate 60 mg). In Phase 3, each participant received randomized exposure to placebo, Hydromorphone (4 and 8 mg), Methylphenidate (30 and 60 mg), tramadol (50, 100, 200, and 400 mg).
Phase 1(6-9 One Day Sessions) Failed to perform study task	7
Phase 1(6-9 One Day Sessions) Withdrawal by Subject	3
Phase 1(6-9 One Day Sessions) Investigator decision	1
Phase 1(6-9 One Day Sessions) Unable to determine	1

Baseline Characteristics

The Discriminative Effects of Tramadol in Humans

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1 n=8 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	40.3 years STANDARD_DEVIATION 2.3 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants

PRIMARY outcome

Timeframe: 1 day

The acquisition of discrimination was to test whether volunteers could identify each training drug condition by the correct letter code. Results are the percentage of correct responses with a range of 0% to 100%.

Outcome measures

Outcome measures
Measure	Hydromorphone 4 mg n=8 Participants	Hydromorphone 8 mg n=8 Participants	Methylphenidate 30 mg	Methylphenidate 60 mg	Tramadol 50 mg	Placebo 0 mg n=8 Participants	Tramadol 100 mg	Tramadol 200 mg	Tramadol 400 mg
Acquisition of Discrimination Assessed by Accuracy of the Discrimination Test	87.5 percent of correct response Interval 0.0 to 100.0	90 percent of correct response Interval 0.0 to 100.0	—	—	—	87 percent of correct response Interval 0.0 to 100.0	—	—	—

PRIMARY outcome

Timeframe: 1 day

Volunteers emitted operant responses on computer keys that corresponded to the training letter, on a fixed interval 1 second schedule for 8.5 minutes. The range is from 0 to 500 operant responses.

Outcome measures

Outcome measures
Measure	Hydromorphone 4 mg n=8 Participants	Hydromorphone 8 mg n=8 Participants	Methylphenidate 30 mg n=8 Participants	Methylphenidate 60 mg n=8 Participants	Tramadol 50 mg n=8 Participants	Placebo 0 mg n=8 Participants	Tramadol 100 mg n=8 Participants	Tramadol 200 mg n=8 Participants	Tramadol 400 mg n=8 Participants
Discrimination Effects Assessed by Operant Responses Placebo	116.6 Responses Standard Error 76.4	0.0 Responses Standard Error 0.0	0.0 Responses Standard Error 0.0	0.0 Responses Standard Error 0.0	464.1 Responses Standard Error 4.2	455.5 Responses Standard Error 9.6	341.3 Responses Standard Error 74.8	86.6 Responses Standard Error 62.0	115.6 Responses Standard Error 75.7
Discrimination Effects Assessed by Operant Responses Hydromorphone	341.3 Responses Standard Error 74.7	453.4 Responses Standard Error 9.0	0.0 Responses Standard Error 0.0	0.0 Responses Standard Error 0.0	0.0 Responses Standard Error 0.0	0.0 Responses Standard Error 0.0	118.1 Responses Standard Error 77.3	367.0 Responses Standard Error 60.2	282.9 Responses Standard Error 83.4
Discrimination Effects Assessed by Operant Responses Methylphenidate	0.0 Responses Standard Error 0.0	0.0 Responses Standard Error 0.0	465.4 Responses Standard Error 4.7	465.8 Responses Standard Error 3.0	0.0 Responses Standard Error 0.0	0.0 Responses Standard Error 0.0	0.0 Responses Standard Error 0.0	0.0 Responses Standard Error 0.0	59.9 Responses Standard Error 59.9

PRIMARY outcome

Timeframe: 1day

In point distribution, volunteers distributed 50 points among three training drug letters depending on how certain they were of the identity of the administrated drug. Maximum total is 50 points.

Outcome measures

Outcome measures
Measure	Hydromorphone 4 mg n=8 Participants	Hydromorphone 8 mg n=8 Participants	Methylphenidate 30 mg n=8 Participants	Methylphenidate 60 mg n=8 Participants	Tramadol 50 mg n=8 Participants	Placebo 0 mg n=8 Participants	Tramadol 100 mg n=8 Participants	Tramadol 200 mg n=8 Participants	Tramadol 400 mg n=8 Participants
Discrimination Effects Assessed by Point Distribution Placebo	11.9 Points distributed Standard Error 7.8	0.0 Points distributed Standard Error 0.0	0.0 Points distributed Standard Error 0.0	0.0 Points distributed Standard Error 0.0	50.0 Points distributed Standard Error 0.0	50.0 Points distributed Standard Error 0.0	37.5 Points distributed Standard Error 8.2	9.4 Points distributed Standard Error 6.6	12.5 Points distributed Standard Error 8.2
Discrimination Effects Assessed by Point Distribution Hydromorphone	38.1 Points distributed Standard Error 7.8	50.0 Points distributed Standard Error 0.0	0.0 Points distributed Standard Error 0.0	0.0 Points distributed Standard Error 0.0	0.0 Points distributed Standard Error 0.0	0.0 Points distributed Standard Error 0.0	12.5 Points distributed Standard Error 8.2	38.3 Points distributed Standard Error 6.5	31.3 Points distributed Standard Error 9.1
Discrimination Effects Assessed by Point Distribution Methylphenidate	0.0 Points distributed Standard Error 0.0	0.0 Points distributed Standard Error 0.0	50.0 Points distributed Standard Error 0.0	50.0 Points distributed Standard Error 0.0	0.0 Points distributed Standard Error 0.0	0.0 Points distributed Standard Error 0.0	0.0 Points distributed Standard Error 0.0	0.0 Points distributed Standard Error 0.0	6.3 Points distributed Standard Error 6.3

PRIMARY outcome

Timeframe: 1 day

During discrete choice, volunteers were given three choices (placebo, hydromorphone, methylphenidate) and were asked to choose which of the training drugs they thought they received. The outcome measure illustrates the percentage of participants who chose either placebo, hydromorphone, or methylphenidate during each drug condition (i.e., Placebo, Hydromorphone 8 mg, Tramadol 50 mg, etc.), ranging from 0-100. The outcome measure represents the percentage of participants who chose either placebo, opioid agonist, or stimulant across each drug condition.

Outcome measures

Outcome measures
Measure	Hydromorphone 4 mg n=8 Participants	Hydromorphone 8 mg n=8 Participants	Methylphenidate 30 mg n=8 Participants	Methylphenidate 60 mg n=8 Participants	Tramadol 50 mg n=8 Participants	Placebo 0 mg n=8 Participants	Tramadol 100 mg n=8 Participants	Tramadol 200 mg n=8 Participants	Tramadol 400 mg n=8 Participants
Discrimination Effects Assessed by Discrete Choice Placebo	25 percentage of drug identification	0 percentage of drug identification	0 percentage of drug identification	0 percentage of drug identification	100 percentage of drug identification	100 percentage of drug identification	75 percentage of drug identification	25 percentage of drug identification	25 percentage of drug identification
Discrimination Effects Assessed by Discrete Choice Hydromorphone	75 percentage of drug identification	100 percentage of drug identification	0 percentage of drug identification	0 percentage of drug identification	0 percentage of drug identification	0 percentage of drug identification	25 percentage of drug identification	75 percentage of drug identification	63 percentage of drug identification
Discrimination Effects Assessed by Discrete Choice Methylphenidate	0 percentage of drug identification	0 percentage of drug identification	100 percentage of drug identification	100 percentage of drug identification	0 percentage of drug identification	0 percentage of drug identification	0 percentage of drug identification	0 percentage of drug identification	12 percentage of drug identification

SECONDARY outcome

Timeframe: Measure at 120 min after drug administration

During the peak (assessed at 120 min) of each drug administration, participants were asked to complete the pharmacological class questionnaire. The pharmacological class questionnaire had volunteers indicate which drug class was most similar to the drug condition they received. Ten drug classes were listed with descriptive labels and examples of each: placebo, opiates (or opioid agonist), phenothiazines, barbiturates, antidepressants, opiate antagonists, hallucinogens, benzodiazepines, stimulants, and other. Of these choices, participants chose 3: placebo, opioid agonist, and stimulant. The outcome measure represents the percentage of participants who chose either placebo, opioid agonist, or stimulant across each drug condition.

Outcome measures

Outcome measures
Measure	Hydromorphone 4 mg n=8 Participants	Hydromorphone 8 mg n=8 Participants	Methylphenidate 30 mg n=8 Participants	Methylphenidate 60 mg n=8 Participants	Tramadol 50 mg n=8 Participants	Placebo 0 mg n=8 Participants	Tramadol 100 mg n=8 Participants	Tramadol 200 mg n=8 Participants	Tramadol 400 mg n=8 Participants
Physiologic Effects Assessed by the Pharmacological Class Questionnaire Placebo	25 percentage of drug identification	0 percentage of drug identification	0 percentage of drug identification	0 percentage of drug identification	100 percentage of drug identification	100 percentage of drug identification	75 percentage of drug identification	37 percentage of drug identification	25 percentage of drug identification
Physiologic Effects Assessed by the Pharmacological Class Questionnaire Opioid Agonist	75 percentage of drug identification	100 percentage of drug identification	0 percentage of drug identification	0 percentage of drug identification	0 percentage of drug identification	0 percentage of drug identification	25 percentage of drug identification	63 percentage of drug identification	63 percentage of drug identification
Physiologic Effects Assessed by the Pharmacological Class Questionnaire Stimulant	0 percentage of drug identification	0 percentage of drug identification	100 percentage of drug identification	100 percentage of drug identification	0 percentage of drug identification	0 percentage of drug identification	0 percentage of drug identification	0 percentage of drug identification	12 percentage of drug identification

SECONDARY outcome

Timeframe: Measure at 120 min after drug administration

Change in pupil diameter (mm) at peak (120 min) compared to baseline measure of pupil diameter

Outcome measures

Outcome measures
Measure	Hydromorphone 4 mg n=8 Participants	Hydromorphone 8 mg n=8 Participants	Methylphenidate 30 mg n=8 Participants	Methylphenidate 60 mg n=8 Participants	Tramadol 50 mg n=8 Participants	Placebo 0 mg n=8 Participants	Tramadol 100 mg n=8 Participants	Tramadol 200 mg n=8 Participants	Tramadol 400 mg n=8 Participants
Physiological Effects Assessed by Peak Change From Baseline Pupil Diameter	-1.2 mm Standard Error 0.2	-1.9 mm Standard Error 0.2	-0.6 mm Standard Error 0.3	-0.3 mm Standard Error 0.2	-0.5 mm Standard Error 0.1	-0.5 mm Standard Error 0.2	-0.2 mm Standard Error 0.1	-0.8 mm Standard Error 0.3	-0.8 mm Standard Error 0.3

SECONDARY outcome

Timeframe: Measure at 120 min after drug administration

The Visual Analog Scale (VAS) measures subjective ratings of opioid agonist effects. The scale on this measure ranges from 0 being "Not at all" to 100 being "Extremely". On this scale, higher scores indicate a stronger drug effect. The outcome measure illustrates a difference from peak (120 min) to baseline measure on VAS.

Outcome measures

Outcome measures
Measure	Hydromorphone 4 mg n=8 Participants	Hydromorphone 8 mg n=8 Participants	Methylphenidate 30 mg n=8 Participants	Methylphenidate 60 mg n=8 Participants	Tramadol 50 mg n=8 Participants	Placebo 0 mg n=8 Participants	Tramadol 100 mg n=8 Participants	Tramadol 200 mg n=8 Participants	Tramadol 400 mg n=8 Participants
Peak Change From Baseline Opioid Agonist Effects Assessed by the Visual Analog Scale (VAS)	2.9 units on a scale Standard Error 1.0	4.8 units on a scale Standard Error 2.1	2.1 units on a scale Standard Error 0.5	3.4 units on a scale Standard Error 1.2	0.4 units on a scale Standard Error 0.4	1.4 units on a scale Standard Error 0.7	1.6 units on a scale Standard Error 0.7	2.1 units on a scale Standard Error 1.0	3.8 units on a scale Standard Error 1.8

SECONDARY outcome

Timeframe: Measure at 120 min after drug administration

The Visual Analog Scale (VAS) measures subjective ratings of stimulant effects. The scale on this measure ranges from 0 being "Not at all" to 100 being "Extremely". On this scale, higher scores indicate a stronger drug effect. The outcome measure illustrates a difference from peak (120 min) to baseline measure.

Outcome measures

Outcome measures
Measure	Hydromorphone 4 mg n=8 Participants	Hydromorphone 8 mg n=8 Participants	Methylphenidate 30 mg n=8 Participants	Methylphenidate 60 mg n=8 Participants	Tramadol 50 mg n=8 Participants	Placebo 0 mg n=8 Participants	Tramadol 100 mg n=8 Participants	Tramadol 200 mg n=8 Participants	Tramadol 400 mg n=8 Participants
Peak Change From Baseline Stimulant Effects Assessed by the Visual Analog Scale (VAS)	3.6 units on a scale Standard Error 1.0	3.6 units on a scale Standard Error 1.2	8.0 units on a scale Standard Error 1.6	10.6 units on a scale Standard Error 2.3	0.6 units on a scale Standard Error 0.4	1.4 units on a scale Standard Error 0.8	0.9 units on a scale Standard Error 0.5	4.9 units on a scale Standard Error 2.0	6.9 units on a scale Standard Error 2.1

Adverse Events

All Participants

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Eric C. Strain, M.D.

Johns Hopkins University School of Medicine

Phone: 410-550-1191

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place