Trial Outcomes & Findings for A Study in Healthy Men to Test Whether BI 409306, BI 425809 or Lamotrigine Can Reverse the Memory Problems Caused by Ketamine (NCT NCT04602221)
NCT ID: NCT04602221
Last Updated: 2024-03-12
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
40 participants
Primary outcome timeframe
At 4:20 and 5:06 hours:minutes after first drug administration in each treatment period.
Results posted on
2024-03-12
Participant Flow
The clinical trial was performed as a randomised, placebo-controlled, double-blind, doubledummy, three-way crossover trial in healthy male subjects to investigate if and to what extent BI 409306, BI 425809, and lamotrigine attenuated ketamine-induced cognitive deficits
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participant milestones
| Measure |
Treatment Sequence: R-T3-T2
Subjects randomized to treatment sequence R-T3-T2 received reference treatment R in period 1, test treatment T3 in period 2 and test treatment T2 in period. Treatments were administered on Day 1 of each treatment period.
R: At 00:00 hours (planned time): one film-coated tablet of Placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride were administered intravenously at 5:00 hours (planned time).
Treatment periods was separated by a washout period of at least 11 days.
|
Treatment Sequence: R-T3-T1
Subjects randomized to treatment sequence R-T3-T1 received reference treatment R in period 1, test treatment T3 in period 2 and test treatment T1 in period 3. Treatments were administered on Day 1 of each treatment period.
R: At 00:00 hours (planned time): one film-coated tablet of Placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: R-T2-T3
Subjects randomized to treatment sequence R-T2-T3 received reference treatment R in period 1, test treatment T2 in period 2 and test treatment T3 in period 3. Treatments were administered on Day 1 of each treatment period.
R: At 00:00 hours (planned time): one film-coated tablet of Placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: R-T2-T1
Subjects randomized to treatment sequence R-T2-T1 received reference treatment R in period 1, test treatment T2 in period 2 and test treatment T1 in period 3. Treatments were administered on Day 1 of each treatment period.
R: At 00:00 hours (planned time): one film-coated tablet of Placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: R-T1-T3
Subjects randomized to treatment sequence R-T1-T3 received reference treatment R in period 1, test treatment T1 in period 2 and test treatment T3 in period 3. Treatments were administered on Day 1 of each treatment period.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: R-T1-T2
Subjects randomized to treatment sequence R-T1-T2 received reference treatment R in period 1, test treatment T1 in period 2 and test treatment T2 in period 3. Treatments were administered on Day 1 of each treatment period.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T3-R-T2
Subjects randomized to treatment sequence T3-R-T2 received test treatment T3 in period 1, reference treatment R in period 2 and test treatment T2 in period 3. Treatments were administered on Day 1 of each treatment period.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T3-R-T1
Subjects randomized to treatment sequence T3-R-T1 received test treatment T3 in period 1, reference treatment R in period 2 and test treatment T1 in period 3. Treatments were administered on Day 1 of each treatment period.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T3-T2-R
Subjects randomized to treatment sequence T3-T2-R received test treatment T3 in period 1, test treatment T2 in period 2 and reference treatment R in period 3. Treatments were administered on Day 1 of each treatment period.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T3-T1-R
Subjects randomized to treatment sequence T3-T1-R received test treatment T3 in period 1, test treatment T1 in period 2 and reference treatment R in period 3. Treatments were administered on Day 1 of each treatment period.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T2-R-T3
Subjects randomized to treatment sequence T2-R-T3 received test treatment T2 in period 1, reference treatment R in period 2 and test treatment T3 in period 3. Treatments were administered on Day 1 of each treatment period.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T2-R-T1
Subjects randomized to treatment sequence T2-R-T1 received test treatment T2 in period 1, reference treatment R in period 2 and test treatment T1 in period 3. Treatments were administered on Day 1 of each treatment period.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T2-T3-R
Subjects randomized to treatment sequence T2-T3-R received test treatment T2 in period 1, test treatment T3 in period 2 and reference treatment R in period 3. Treatments were administered on Day 1 of each treatment period.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T2-T1-R
Subjects randomized to treatment sequence T2-T1-R received test treatment T2 in period 1, test treatment T1 in period 2 and reference treatment R in period 3. Treatments were administered on Day 1 of each treatment period.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T1-R-T3
Subjects randomized to treatment sequence T1-R-T3 received test treatment T1 in period 1, reference treatment R in period 2 and test treatment T3 in period 3. Treatments were administered on Day 1 of each treatment period.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T1-R-T2
Subjects randomized to treatment sequence T1-R-T2 received test treatment T1 in period 1, reference treatment R in period 2 and test treatment T2 in period 3. Treatments were administered on Day 1 of each treatment period.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T1-T3-R
Subjects randomized to treatment sequence T1-T3-R received test treatment T1 in period 1, test treatment T3 in period 2 and reference treatment R in period 3. Treatments were administered on Day 1 of each treatment period.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T1-T2-R
Subjects randomized to treatment sequence T1-T2-R received test treatment T1 in period 1, test treatment T2 in period 2 and reference treatment R in period 3. Treatments were administered on Day 1 of each treatment period.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
3
|
2
|
2
|
3
|
2
|
3
|
|
Overall Study
COMPLETED
|
3
|
2
|
1
|
2
|
2
|
1
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
1
|
0
|
1
|
Reasons for withdrawal
| Measure |
Treatment Sequence: R-T3-T2
Subjects randomized to treatment sequence R-T3-T2 received reference treatment R in period 1, test treatment T3 in period 2 and test treatment T2 in period. Treatments were administered on Day 1 of each treatment period.
R: At 00:00 hours (planned time): one film-coated tablet of Placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride were administered intravenously at 5:00 hours (planned time).
Treatment periods was separated by a washout period of at least 11 days.
|
Treatment Sequence: R-T3-T1
Subjects randomized to treatment sequence R-T3-T1 received reference treatment R in period 1, test treatment T3 in period 2 and test treatment T1 in period 3. Treatments were administered on Day 1 of each treatment period.
R: At 00:00 hours (planned time): one film-coated tablet of Placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: R-T2-T3
Subjects randomized to treatment sequence R-T2-T3 received reference treatment R in period 1, test treatment T2 in period 2 and test treatment T3 in period 3. Treatments were administered on Day 1 of each treatment period.
R: At 00:00 hours (planned time): one film-coated tablet of Placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: R-T2-T1
Subjects randomized to treatment sequence R-T2-T1 received reference treatment R in period 1, test treatment T2 in period 2 and test treatment T1 in period 3. Treatments were administered on Day 1 of each treatment period.
R: At 00:00 hours (planned time): one film-coated tablet of Placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: R-T1-T3
Subjects randomized to treatment sequence R-T1-T3 received reference treatment R in period 1, test treatment T1 in period 2 and test treatment T3 in period 3. Treatments were administered on Day 1 of each treatment period.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: R-T1-T2
Subjects randomized to treatment sequence R-T1-T2 received reference treatment R in period 1, test treatment T1 in period 2 and test treatment T2 in period 3. Treatments were administered on Day 1 of each treatment period.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T3-R-T2
Subjects randomized to treatment sequence T3-R-T2 received test treatment T3 in period 1, reference treatment R in period 2 and test treatment T2 in period 3. Treatments were administered on Day 1 of each treatment period.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T3-R-T1
Subjects randomized to treatment sequence T3-R-T1 received test treatment T3 in period 1, reference treatment R in period 2 and test treatment T1 in period 3. Treatments were administered on Day 1 of each treatment period.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T3-T2-R
Subjects randomized to treatment sequence T3-T2-R received test treatment T3 in period 1, test treatment T2 in period 2 and reference treatment R in period 3. Treatments were administered on Day 1 of each treatment period.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T3-T1-R
Subjects randomized to treatment sequence T3-T1-R received test treatment T3 in period 1, test treatment T1 in period 2 and reference treatment R in period 3. Treatments were administered on Day 1 of each treatment period.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T2-R-T3
Subjects randomized to treatment sequence T2-R-T3 received test treatment T2 in period 1, reference treatment R in period 2 and test treatment T3 in period 3. Treatments were administered on Day 1 of each treatment period.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T2-R-T1
Subjects randomized to treatment sequence T2-R-T1 received test treatment T2 in period 1, reference treatment R in period 2 and test treatment T1 in period 3. Treatments were administered on Day 1 of each treatment period.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T2-T3-R
Subjects randomized to treatment sequence T2-T3-R received test treatment T2 in period 1, test treatment T3 in period 2 and reference treatment R in period 3. Treatments were administered on Day 1 of each treatment period.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T2-T1-R
Subjects randomized to treatment sequence T2-T1-R received test treatment T2 in period 1, test treatment T1 in period 2 and reference treatment R in period 3. Treatments were administered on Day 1 of each treatment period.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T1-R-T3
Subjects randomized to treatment sequence T1-R-T3 received test treatment T1 in period 1, reference treatment R in period 2 and test treatment T3 in period 3. Treatments were administered on Day 1 of each treatment period.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T1-R-T2
Subjects randomized to treatment sequence T1-R-T2 received test treatment T1 in period 1, reference treatment R in period 2 and test treatment T2 in period 3. Treatments were administered on Day 1 of each treatment period.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T1-T3-R
Subjects randomized to treatment sequence T1-T3-R received test treatment T1 in period 1, test treatment T3 in period 2 and reference treatment R in period 3. Treatments were administered on Day 1 of each treatment period.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose.
At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
T3: At 0:00 hours (planned time): one film-coated tablet of 25 mg BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of placebo to BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
Treatment Sequence: T1-T2-R
Subjects randomized to treatment sequence T1-T2-R received test treatment T1 in period 1, test treatment T2 in period 2 and reference treatment R in period 3. Treatments were administered on Day 1 of each treatment period.
T1: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): three tablets of 100 mg Lamotrigine and one film-coated tablet of placebo to BI 409306 as single oral dose each.
T2: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809, as single oral dose. At 03:00 hours (planned time): one film-coated tablet of 50 mg BI 409306 and three film coated tablets of placebo to lamotrigine, as single oral dose each.
R: At 00:00 hours (planned time): one film-coated tablet of placebo to BI 425809 as single oral dose. At 03:00 hours (planned time): three film-coated tablets of placebo to lamotrigine and one film-coated tablet of placebo to BI 409306, as single oral dose each.
In each treatment period 500 mg/10 milliliter solution for injection of Ketamine hydrochloride was administered intravenously at 5:00 hours (planned time). Treatment periods were separated by a washout period of at least 11 days.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
Discontinuation of trial treatment
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
Other than listed
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Baseline Characteristics
A Study in Healthy Men to Test Whether BI 409306, BI 425809 or Lamotrigine Can Reverse the Memory Problems Caused by Ketamine
Baseline characteristics by cohort
| Measure |
Total
n=40 Participants
All participants that were treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
|---|---|
|
Age, Continuous
|
36.9 Years
STANDARD_DEVIATION 8.7 • n=99 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
40 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
34 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
17 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: At 4:20 and 5:06 hours:minutes after first drug administration in each treatment period.Population: Pharmacodynamic (PD) set (PDS): PD analyses were based on the PDS which was defined as all randomised subjects who performed the post ketamine tests in at least one period. Number of participants differs due to incomplete crossover design.
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.
Outcome measures
| Measure |
Placebo (R)
n=34 Participants
One film-coated tablet of Placebo to BI 409306 and three film-coated tablets of placebo to lamotrigine were administered as oral single dose each, 2 hours prior to ketamine infusion on Day 1 and one film-coated tablet of Placebo to BI 425809 was administered as oral single dose 5 hours prior to ketamine infusion on Day 1.
|
25 mg BI 425809 (T3)
n=23 Participants
1 film-coated tablet of 25 milligrams (mg) BI 425809 was administered orally once daily with 240 mL of water after a light snack on Day 1 of treatment T3, 5 hours prior to ketamine infusion.
|
50 mg BI 409306 (T2)
n=23 Participants
1 film-coated tablet of 50 milligrams (mg) BI 409306 was administered orally once daily with 240 mL of water after a light snack on Day 1 of treatment T2, 2 hours prior to ketamine infusion.
|
300 mg Lamotrigine (T1)
n=26 Participants
3 tablets of 100 milligrams (mg) Lamotrigine were administered orally once daily (daily dose: 300 mg) with 240 mL of water after a light snack on Day 1 of treatment T1, 2 hours prior to ketamine infusion.
|
|---|---|---|---|---|
|
Paired Associate Learning (PAL) Total Errors Adjusted (PALTEA28) on Ketamine
|
24.169 Errors
Standard Error 2.5972
|
23.829 Errors
Standard Error 3.2275
|
28.170 Errors
Standard Error 3.2334
|
22.911 Errors
Standard Error 3.0850
|
SECONDARY outcome
Timeframe: At 4:20 and 5:06 hours:minutes after first drug administration in each treatment period.Population: Pharmacodynamic (PD) set (PDS): PD analyses were based on the PDS which was defined as all randomised subjects who performed the post ketamine tests in at least one period. Number of participants differs due to incomplete crossover design.
SWM assesses the ability of the participant to retain spatial information and manipulate it in working memory. A number of coloured boxes are presented on the screen, and the computer hides a token in these boxes one at a time. The participant is instructed to touch the boxes in turn to search for the token that has been hidden. The key task instruction is that the computer will never hide a token in the same coloured box twice in the same problem. The SWMBE468 evaluates the number of times the subject incorrectly revisits a box in which a token has previously been found. Calculated across all assessed four, six and eight token trials.
Outcome measures
| Measure |
Placebo (R)
n=33 Participants
One film-coated tablet of Placebo to BI 409306 and three film-coated tablets of placebo to lamotrigine were administered as oral single dose each, 2 hours prior to ketamine infusion on Day 1 and one film-coated tablet of Placebo to BI 425809 was administered as oral single dose 5 hours prior to ketamine infusion on Day 1.
|
25 mg BI 425809 (T3)
n=23 Participants
1 film-coated tablet of 25 milligrams (mg) BI 425809 was administered orally once daily with 240 mL of water after a light snack on Day 1 of treatment T3, 5 hours prior to ketamine infusion.
|
50 mg BI 409306 (T2)
n=22 Participants
1 film-coated tablet of 50 milligrams (mg) BI 409306 was administered orally once daily with 240 mL of water after a light snack on Day 1 of treatment T2, 2 hours prior to ketamine infusion.
|
300 mg Lamotrigine (T1)
n=25 Participants
3 tablets of 100 milligrams (mg) Lamotrigine were administered orally once daily (daily dose: 300 mg) with 240 mL of water after a light snack on Day 1 of treatment T1, 2 hours prior to ketamine infusion.
|
|---|---|---|---|---|
|
Spatial Working Memory (SWM) Between Errors (BE468) on Ketamine
|
15.684 Errors
Standard Error 1.3412
|
16.032 Errors
Standard Error 1.5427
|
14.600 Errors
Standard Error 1.5704
|
12.826 Errors
Standard Error 1.5005
|
SECONDARY outcome
Timeframe: At 4:20 and 5:06 hours:minutes after first drug administration in each treatment period.Population: Pharmacodynamic (PD) set (PDS): PD analyses were based on the PDS which was defined as all randomised subjects who performed the post ketamine tests in at least one period. Number of participants differs due to incomplete crossover design.
Rapid Visual Information Processing (RVP) is a sensitive measure of sustained attention, outputting measures of response accuracy, target sensitivity and reaction times. The RVPA is a quantitative measure for a subject's sensitivity to the target sequence regardless of response tendency. The RVPA ranges from 0.00 to 1.00. The higher the RVPA value, the better the sensitivity to the target sequence one has.
Outcome measures
| Measure |
Placebo (R)
n=34 Participants
One film-coated tablet of Placebo to BI 409306 and three film-coated tablets of placebo to lamotrigine were administered as oral single dose each, 2 hours prior to ketamine infusion on Day 1 and one film-coated tablet of Placebo to BI 425809 was administered as oral single dose 5 hours prior to ketamine infusion on Day 1.
|
25 mg BI 425809 (T3)
n=23 Participants
1 film-coated tablet of 25 milligrams (mg) BI 425809 was administered orally once daily with 240 mL of water after a light snack on Day 1 of treatment T3, 5 hours prior to ketamine infusion.
|
50 mg BI 409306 (T2)
n=23 Participants
1 film-coated tablet of 50 milligrams (mg) BI 409306 was administered orally once daily with 240 mL of water after a light snack on Day 1 of treatment T2, 2 hours prior to ketamine infusion.
|
300 mg Lamotrigine (T1)
n=26 Participants
3 tablets of 100 milligrams (mg) Lamotrigine were administered orally once daily (daily dose: 300 mg) with 240 mL of water after a light snack on Day 1 of treatment T1, 2 hours prior to ketamine infusion.
|
|---|---|---|---|---|
|
Rapid Visual Information Processing A' Prime (RVPA) on Ketamine
|
0.8743 Score on a scale
Standard Error 0.00702
|
0.8796 Score on a scale
Standard Error 0.00807
|
0.8800 Score on a scale
Standard Error 0.00810
|
0.9075 Score on a scale
Standard Error 0.00782
|
Adverse Events
Placebo (R)
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
25mg BI 425809 (T3)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
50mg BI 409306 (T2)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
300 mg Lamotrigine (T1)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo (R)
n=37 participants at risk
One film-coated tablet of Placebo to BI 409306 and three film-coated tablets of placebo to lamotrigine were administered as oral single dose each, 2 hours prior to ketamine infusion on Day 1 and one film-coated tablet of Placebo to BI 425809 was administered as oral single dose 5 hours prior to ketamine infusion on Day 1.
|
25mg BI 425809 (T3)
n=24 participants at risk
1 film-coated tablet of 25 milligrams (mg) BI 425809 was administered orally once daily with 240 mL of water after a light snack on Day 1 of treatment T3, 5 hours prior to ketamine infusion.
|
50mg BI 409306 (T2)
n=25 participants at risk
1 film-coated tablet of 50 milligrams (mg) BI 409306 was administered orally once daily with 240 mL of water after a light snack on Day 1 of treatment T2, 2 hours prior to ketamine infusion.
|
300 mg Lamotrigine (T1)
n=26 participants at risk
3 tablets of 100 milligrams (mg) Lamotrigine were administered orally once daily (daily dose: 300 mg) with 240 mL of water after a light snack on Day 1 of treatment T1, 2 hours prior to ketamine infusion.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
5.4%
2/37 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
16.7%
4/24 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
16.0%
4/25 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
3.8%
1/26 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
|
Gastrointestinal disorders
Vomiting
|
8.1%
3/37 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
8.3%
2/24 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
12.0%
3/25 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
3.8%
1/26 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
|
Gastrointestinal disorders
Diarrhoea
|
5.4%
2/37 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
0.00%
0/24 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
0.00%
0/25 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
0.00%
0/26 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
|
Nervous system disorders
Somnolence
|
10.8%
4/37 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
4.2%
1/24 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
0.00%
0/25 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
3.8%
1/26 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
|
Psychiatric disorders
Euphoric mood
|
8.1%
3/37 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
8.3%
2/24 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
0.00%
0/25 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
3.8%
1/26 • From intake of first study drug (00:00h planned time) up to Day 11 (03:00h planned time); Residual Effect Period (REP) of 11 days was used for each study treatment.
Treated Set: The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER