A Randomized, Placebo Controlled, Double-blind, Double-dummy Three-way Cross Over Trial to Investigate the Effect of BI 409306, BI 425809 and Lamotrigine on Ketamine-induced Cognitive Deficits in Healthy Male Subjects
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 40
- Locations
- 2
- Primary Endpoint
- Paired Associate Learning (PAL) Total Errors Adjusted (PALTEA28) on Ketamine
Study Overview
Brief Summary
The main objective of this trail is to investigate if and to what extent BI 409306, BI 425809 and lamotrigine attenuate ketamine induced cognitive deficits.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Healthy male subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
- •Age of 18 to 55 years (inclusive)
- •BMI of 18.5 to 32 kg/m2 (inclusive)
- •Signed and dated written informed consent prior to admission to the study, in accordance with GCP and local legislation
- •Male subjects who meet any of the following criteria from at least 30 days before the first administration of trial medication until 30 days after trial completion:
- •Use of adequate contraception, e.g. use of condom (male subjects) plus any of the following methods (female partners): intrauterine device, hormonal contraception (e.g. implants, injectables, combined oral or vaginal contraceptives) that started at least 2 months prior to first drug administration, or barrier method (e.g. diaphragm with spermicide)
- •Sexually abstinent
- •Vasectomised (vasectomy at least 1 year prior to enrolment)
- •Surgically sterilised female partner (including hysterectomy, bilateral tubal occlusion or bilateral oophorectomy)
- •Postmenopausal female partner, defined as at least 1 year of spontaneous amenorrhea
Exclusion Criteria
- •Any finding in the medical examination (including ECG) deviating from normal and assessed as clinically relevant by the investigator
- •Repeated measurement of systolic blood pressure outside the range of 100 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 bpm
- •Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
- •Any evidence of a concomitant disease assessed as clinically relevant by the investigator
- •Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- •Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
- •History of diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
- •History of relevant orthostatic hypotension, fainting spells, or blackouts Further exclusion criteria apply
Arms & Interventions
Treatment sequence: T1-T3-R
Intervention: Placebo (Drug)
Treatment sequence: T3-T1-R
Intervention: Lamotrigine (Drug)
Treatment sequence: T3-T1-R
Intervention: Placebo (Drug)
Treatment sequence: T1-T2-R
Treatments:
T1: Lamotrigine T2: BI 409306 T3: BI 425809 R: Placebo
Intervention: Lamotrigine (Drug)
Treatment sequence: T1-T2-R
Treatments:
T1: Lamotrigine T2: BI 409306 T3: BI 425809 R: Placebo
Intervention: BI 409306 (Drug)
Treatment sequence: T1-T2-R
Treatments:
T1: Lamotrigine T2: BI 409306 T3: BI 425809 R: Placebo
Intervention: Placebo (Drug)
Treatment sequence: T1-R-T2
Intervention: Lamotrigine (Drug)
Treatment sequence: T1-R-T2
Intervention: BI 409306 (Drug)
Treatment sequence: T1-R-T2
Intervention: Placebo (Drug)
Treatment sequence: T1-T3-R
Intervention: Lamotrigine (Drug)
Treatment sequence: T1-T3-R
Intervention: BI 425809 (Drug)
Treatment sequence: T1-R-T3
Intervention: Lamotrigine (Drug)
Treatment sequence: T1-R-T3
Intervention: Placebo (Drug)
Treatment sequence: T1-R-T3
Intervention: BI 425809 (Drug)
Treatment sequence: T2-T1-R
Intervention: Lamotrigine (Drug)
Treatment sequence: T2-T1-R
Intervention: BI 409306 (Drug)
Treatment sequence: T2-T1-R
Intervention: Placebo (Drug)
Treatment sequence: T2-R-T1
Intervention: Lamotrigine (Drug)
Treatment sequence: T2-R-T1
Intervention: BI 409306 (Drug)
Treatment sequence: T2-R-T1
Intervention: Placebo (Drug)
Treatment sequence: T2-T3-R
Intervention: BI 409306 (Drug)
Treatment sequence: T2-T3-R
Intervention: Placebo (Drug)
Treatment sequence: T2-T3-R
Intervention: BI 425809 (Drug)
Treatment sequence: T2-R-T3
Intervention: BI 409306 (Drug)
Treatment sequence: T2-R-T3
Intervention: Placebo (Drug)
Treatment sequence: T2-R-T3
Intervention: BI 425809 (Drug)
Treatment sequence: T3-R-T1
Intervention: Lamotrigine (Drug)
Treatment sequence: T3-R-T1
Intervention: Placebo (Drug)
Treatment sequence: T3-R-T1
Intervention: BI 425809 (Drug)
Treatment sequence: T3-T1-R
Intervention: BI 425809 (Drug)
Treatment sequence: T3-T2-R
Intervention: BI 409306 (Drug)
Treatment sequence: T3-T2-R
Intervention: Placebo (Drug)
Treatment sequence: T3-T2-R
Intervention: BI 425809 (Drug)
Treatment sequence: T3-R-T2
Intervention: BI 409306 (Drug)
Treatment sequence: T3-R-T2
Intervention: Placebo (Drug)
Treatment sequence: T3-R-T2
Intervention: BI 425809 (Drug)
Treatment sequence: R-T1-T2
Intervention: Lamotrigine (Drug)
Treatment sequence: R-T1-T2
Intervention: BI 409306 (Drug)
Treatment sequence: R-T1-T2
Intervention: Placebo (Drug)
Treatment sequence: R-T2-T1
Intervention: Lamotrigine (Drug)
Treatment sequence: R-T2-T1
Intervention: BI 409306 (Drug)
Treatment sequence: R-T2-T1
Intervention: Placebo (Drug)
Treatment sequence: R-T1-T3
Intervention: Lamotrigine (Drug)
Treatment sequence: R-T1-T3
Intervention: Placebo (Drug)
Treatment sequence: R-T1-T3
Intervention: BI 425809 (Drug)
Treatment sequence: R-T3-T1
Intervention: Lamotrigine (Drug)
Treatment sequence: R-T3-T1
Intervention: Placebo (Drug)
Treatment sequence: R-T3-T1
Intervention: BI 425809 (Drug)
Treatment sequence: R-T2-T3
Intervention: BI 409306 (Drug)
Treatment sequence: R-T2-T3
Intervention: Placebo (Drug)
Treatment sequence: R-T2-T3
Intervention: BI 425809 (Drug)
Treatment sequence: R-T3-T2
Intervention: BI 409306 (Drug)
Treatment sequence: R-T3-T2
Intervention: Placebo (Drug)
Treatment sequence: R-T3-T2
Intervention: BI 425809 (Drug)
Outcomes
Primary Outcomes
Paired Associate Learning (PAL) Total Errors Adjusted (PALTEA28) on Ketamine
Time Frame: At 4:20 and 5:06 hours:minutes after first drug administration in each treatment period.
Paired Associate Learning (PAL) assesses visual memory and new learning. Boxes are displayed on the screen and open in turn to reveal a number of patterns. Participants are instructed to try to remember the location in which each pattern was shown. After all the boxes have been opened, each pattern is then shown in the center of the screen in a randomised order, and the participant touches the box in which the pattern was located. If an error is made, all the patterns are re-presented to remind the participant of their locations. The PALTEA28 evaluates the number of errors committed by the subject plus an adjustment for the estimated number of errors they would have made on any stages that were not reached. Calculated across all assessed two, four, six and eight box trials.
Secondary Outcomes
- Spatial Working Memory (SWM) Between Errors (BE468) on Ketamine(At 4:20 and 5:06 hours:minutes after first drug administration in each treatment period.)
- Rapid Visual Information Processing A' Prime (RVPA) on Ketamine(At 4:20 and 5:06 hours:minutes after first drug administration in each treatment period.)