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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment sequence: T1-T2-R | Experimental | Treatments: T1: Lamotrigine T2: BI 409306 T3: BI 425809 R: Placebo |
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| Treatment sequence: T1-R-T2 | Experimental |
| |
| Treatment sequence: T1-T3-R | Experimental |
| |
| Treatment sequence: T1-R-T3 | Experimental |
| |
| Treatment sequence: T2-T1-R | Experimental |
| |
| Treatment sequence: T2-R-T1 | Experimental |
| |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lamotrigine | Drug | Tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| Paired Associate Learning (PAL) Total Errors Adjusted (PALTEA28) on Ketamine | 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. | At 4:20 and 5:06 hours:minutes after first drug administration in each treatment period. |
| Measure | Description | Time Frame |
|---|---|---|
| Spatial Working Memory (SWM) Between Errors (BE468) on Ketamine | 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. |
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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:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Collaborative Neuroscience Research, LLC | Long Beach | California | 90806 | United States | ||
| Hassman Research Institute |
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| Label | URL |
|---|---|
| Related Info | View source |
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Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:
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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.
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
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| FG005 | 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. |
| FG006 | 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. |
| FG007 | 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. |
| FG008 | 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. |
| FG009 | 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. |
| FG010 | 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. |
| FG011 | 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. |
| FG012 | 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. |
| FG013 | 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. |
| FG014 | 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. |
| FG015 | 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. |
| FG016 | 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. |
| FG017 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Treated set (TS): The treated set included all subjects who were randomised and treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine.
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| ID | Title | Description |
|---|---|---|
| BG000 | Total | All participants that were treated with at least one dose of Investigational medicinal product (IMP)/Placebo or ketamine. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Paired Associate Learning (PAL) Total Errors Adjusted (PALTEA28) on Ketamine | 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. | 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. | Posted | Least Squares Mean | Standard Error | Errors | At 4:20 and 5:06 hours:minutes after first drug administration in each treatment period. |
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo (R) | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim | 18002430127 | clintriage.rdg@boehringer-ingelheim.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 12, 2021 | Aug 10, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 14, 2022 | Aug 10, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000077213 | Lamotrigine |
| C000630656 | BI 409306 |
| C000634404 | BI 425809 |
| ID | Term |
|---|---|
| D014227 | Triazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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3-treatment period design
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| Treatment sequence: T2-T3-R |
| Experimental |
|
| Treatment sequence: T2-R-T3 | Experimental |
|
| Treatment sequence: T3-R-T1 | Experimental |
|
| Treatment sequence: T3-T1-R | Experimental |
|
| Treatment sequence: T3-T2-R | Experimental |
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| Treatment sequence: T3-R-T2 | Experimental |
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| Treatment sequence: R-T1-T2 | Experimental |
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| Treatment sequence: R-T2-T1 | Experimental |
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| Treatment sequence: R-T1-T3 | Experimental |
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| Treatment sequence: R-T3-T1 | Experimental |
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| Treatment sequence: R-T2-T3 | Experimental |
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| Treatment sequence: R-T3-T2 | Experimental |
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| BI 409306 | Drug | Film-coated tablet |
|
| Placebo | Drug | Tablet, Film-coated tablet |
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| BI 425809 | Drug | Film-coated tablet |
|
| 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 | 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. | At 4:20 and 5:06 hours:minutes after first drug administration in each treatment period. |
| Marlton |
| New Jersey |
| 08053 |
| United States |
| Other than listed |
|
| Withdrawal by Subject |
|
| Lost to Follow-up |
|
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Placebo (R) | 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. |
| OG001 | 25 mg BI 425809 (T3) | 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. |
| OG002 | 50 mg BI 409306 (T2) | 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. |
| OG003 | 300 mg Lamotrigine (T1) | 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. |
|
|
|
| Secondary | Spatial Working Memory (SWM) Between Errors (BE468) on Ketamine | 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. | 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. | Posted | Least Squares Mean | Standard Error | Errors | At 4:20 and 5:06 hours:minutes after first drug administration in each treatment period. |
|
|
|
|
| Secondary | Rapid Visual Information Processing A' Prime (RVPA) on Ketamine | 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. | 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. | Posted | Least Squares Mean | Standard Error | Score on a scale | At 4:20 and 5:06 hours:minutes after first drug administration in each treatment period. |
|
|
|
|
| 0 |
| 37 |
| 0 |
| 37 |
| 10 |
| 37 |
| EG001 | 25mg BI 425809 (T3) | 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. | 0 | 24 | 0 | 24 | 5 | 24 |
| EG002 | 50mg BI 409306 (T2) | 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. | 0 | 25 | 0 | 25 | 5 | 25 |
| EG003 | 300 mg Lamotrigine (T1) | 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. | 0 | 26 | 0 | 26 | 2 | 26 |
| Vomiting | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
|
| Euphoric mood | Psychiatric disorders | MedDRA 25.0 | Systematic Assessment |
|
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.
| A linear mixed effects model, i.e. analyses of covariance (ANCOVA) was used for analysis of the secondary endpoint. This model included effects for sequence, subject within sequence, period, baseline values (pre-ketamine baseline and on-ketamine baseline) and treatment. The effect 'subject within sequence' were considered as random, whereas the other effects were considered as fixed. | ANCOVA | 0.4973 | Difference of adjusted means | -1.085 | Standard Error of the Mean | 1.5889 | 2-Sided | 95 | -4.260 | 2.091 | The difference was calculated as treatment group minus placebo group. | Other |
| A linear mixed effects model, i.e. analyses of covariance (ANCOVA) was used for analysis of the secondary endpoint. This model included effects for sequence, subject within sequence, period, baseline values (pre-ketamine baseline and on-ketamine baseline) and treatment. The effect 'subject within sequence' were considered as random, whereas the other effects were considered as fixed. | ANCOVA | 0.0658 | Difference of adjusted means | -2.858 | Standard Error of the Mean | 1.5266 | 2-Sided | 95 | -5.909 | 0.192 | The difference was calculated as treatment group minus placebo group. | Other |
| A linear mixed effects model, i.e. analyses of covariance (ANCOVA) was used for analysis of the secondary endpoint. This model included effects for sequence, subject within sequence, period, baseline values (pre-ketamine baseline and on-ketamine baseline) and treatment. The effect 'subject within sequence' were considered as random, whereas the other effects were considered as fixed. | ANCOVA | 0.4723 | Difference of adjusted means | 0.0058 | Standard Error of the Mean | 0.00798 | 2-Sided | 95 | -0.0102 | 0.0217 | The difference was calculated as treatment group minus placebo group. | Other |
| A linear mixed effects model, i.e. analyses of covariance (ANCOVA) was used for analysis of the secondary endpoint. This model included effects for sequence, subject within sequence, period, baseline values (pre-ketamine baseline and on-ketamine baseline) and treatment. The effect 'subject within sequence' were considered as random, whereas the other effects were considered as fixed. | ANCOVA | < .0001 | Difference of adjusted means | 0.0333 | Standard Error of the Mean | 0.00767 | 2-Sided | 95 | 0.0180 | 0.0486 | The difference was calculated as treatment group minus placebo group. | Other |