A Study in Healthy Men to Test Whether BI 409306, BI 425809 or Lamotrigine Can Reverse the Memory Problems Caused by Ketamine

A Randomized, Placebo Controlled, Double-blind, Double-dummy Three-way Cross Over Trial to Investigate the Effect of BI 409306, BI 425809 and Lamotrigine on Ketamine-induced Cognitive Deficits in Healthy Male Subjects

The main objective of this trail is to investigate if and to what extent BI 409306, BI 425809 and lamotrigine attenuate ketamine induced cognitive deficits.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Lamotrigine; Drug: BI 409306; Drug: Placebo; Drug: BI 425809

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Research, LLC
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Hassman Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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
2. Age of 18 to 55 years (inclusive)
3. BMI of 18.5 to 32 kg/m2 (inclusive)
4. Signed and dated written informed consent prior to admission to the study, in accordance with GCP and local legislation

5. Male subjects who meet any of the following criteria from at least 30 days before the first administration of trial medication until 30 days after trial completion:

   • Use of adequate contraception, e.g. use of condom (male subjects) plus any of the following methods (female partners): intrauterine device, hormonal contraception (e.g. implants, injectables, combined oral or vaginal contraceptives) that started at least 2 months prior to first drug administration, or barrier method (e.g. diaphragm with spermicide)
   • Sexually abstinent
   • Vasectomised (vasectomy at least 1 year prior to enrolment)
   • Surgically sterilised female partner (including hysterectomy, bilateral tubal occlusion or bilateral oophorectomy)
   • Postmenopausal female partner, defined as at least 1 year of spontaneous amenorrhea

Exclusion Criteria:

1. Any finding in the medical examination (including ECG) deviating from normal and assessed as clinically relevant by the investigator
2. Repeated measurement of systolic blood pressure outside the range of 100 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 bpm
3. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
4. Any evidence of a concomitant disease assessed as clinically relevant by the investigator
5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
6. Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
7. History of diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
8. History of relevant orthostatic hypotension, fainting spells, or blackouts Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

18

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment sequence: T1-T2-R; Treatments: T1: Lamotrigine T2: BI 409306 T3: BI 425809 R: Placebo	Drug: Lamotrigine; Tablet; Drug: BI 409306; Film-coated tablet; Drug: Placebo; Tablet, Film-coated tablet
Experimental: Treatment sequence: T1-R-T2	Drug: Lamotrigine; Tablet; Drug: BI 409306; Film-coated tablet; Drug: Placebo; Tablet, Film-coated tablet
Experimental: Treatment sequence: T1-T3-R	Drug: Lamotrigine; Tablet; Drug: Placebo; Tablet, Film-coated tablet; Drug: BI 425809; Film-coated tablet
Experimental: Treatment sequence: T1-R-T3	Drug: Lamotrigine; Tablet; Drug: Placebo; Tablet, Film-coated tablet; Drug: BI 425809; Film-coated tablet
Experimental: Treatment sequence: T2-T1-R	Drug: Lamotrigine; Tablet; Drug: BI 409306; Film-coated tablet; Drug: Placebo; Tablet, Film-coated tablet
Experimental: Treatment sequence: T2-R-T1	Drug: Lamotrigine; Tablet; Drug: BI 409306; Film-coated tablet; Drug: Placebo; Tablet, Film-coated tablet
Experimental: Treatment sequence: T2-T3-R	Drug: BI 409306; Film-coated tablet; Drug: Placebo; Tablet, Film-coated tablet; Drug: BI 425809; Film-coated tablet
Experimental: Treatment sequence: T2-R-T3	Drug: BI 409306; Film-coated tablet; Drug: Placebo; Tablet, Film-coated tablet; Drug: BI 425809; Film-coated tablet
Experimental: Treatment sequence: T3-R-T1	Drug: Lamotrigine; Tablet; Drug: Placebo; Tablet, Film-coated tablet; Drug: BI 425809; Film-coated tablet
Experimental: Treatment sequence: T3-T1-R	Drug: Lamotrigine; Tablet; Drug: Placebo; Tablet, Film-coated tablet; Drug: BI 425809; Film-coated tablet
Experimental: Treatment sequence: T3-T2-R	Drug: BI 409306; Film-coated tablet; Drug: Placebo; Tablet, Film-coated tablet; Drug: BI 425809; Film-coated tablet
Experimental: Treatment sequence: T3-R-T2	Drug: BI 409306; Film-coated tablet; Drug: Placebo; Tablet, Film-coated tablet; Drug: BI 425809; Film-coated tablet
Experimental: Treatment sequence: R-T1-T2	Drug: Lamotrigine; Tablet; Drug: BI 409306; Film-coated tablet; Drug: Placebo; Tablet, Film-coated tablet
Experimental: Treatment sequence: R-T2-T1	Drug: Lamotrigine; Tablet; Drug: BI 409306; Film-coated tablet; Drug: Placebo; Tablet, Film-coated tablet
Experimental: Treatment sequence: R-T1-T3	Drug: Lamotrigine; Tablet; Drug: Placebo; Tablet, Film-coated tablet; Drug: BI 425809; Film-coated tablet
Experimental: Treatment sequence: R-T3-T1	Drug: Lamotrigine; Tablet; Drug: Placebo; Tablet, Film-coated tablet; Drug: BI 425809; Film-coated tablet
Experimental: Treatment sequence: R-T2-T3	Drug: BI 409306; Film-coated tablet; Drug: Placebo; Tablet, Film-coated tablet; Drug: BI 425809; Film-coated tablet
Experimental: Treatment sequence: R-T3-T2	Drug: BI 409306; Film-coated tablet; Drug: Placebo; Tablet, Film-coated tablet; Drug: BI 425809; Film-coated tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.

Secondary Outcome Measures

Outcome Measure	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.	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.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Actual): August 1, 2022
• Study Completion (Actual): August 12, 2022

Study Registration Dates

• First Submitted: October 16, 2020
• First Submitted That Met QC Criteria: October 20, 2020
• First Posted (Actual): October 26, 2020

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anticonvulsants; Sodium Channel Blockers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Phosphodiesterase Inhibitors; Nootropic Agents; Lamotrigine; BI 425809; BI 409306
• Other Study ID Numbers: 1289-0057

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

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:

1. studies in products where Boehringer Ingelheim is not the license holder;
2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No