A Study in Healthy Men to Test Whether BI 474121 Can Reverse the Memory Problems Caused by Ketamine

A Randomized, Placebo Controlled, Double-blind, Double-dummy, Three-way Crossover Trial to Investigate the Effect of Two Doses of BI 474121 on Ketamine Induced Cognitive Deficits in Healthy Male Subjects

To investigate the effect of BI 474121 compared to placebo on ketamine-induced cognitive deficits to predict efficacy in patients with cognitive disorders.

Study Overview

• Status: Withdrawn
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BI 474121; Drug: Ketamine hydrochloride

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests
• Age of 18 to 55 years (inclusive)
• Body mass index (BMI) of 18.5 to 32 kg/m2 (inclusive)
• Signed and dated written informed consent(s) prior to admission to the study, in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
• If men who are able to father a child, are willing to participate, they have to use an adequate form of effective contraception for the duration of study participation and for at least 30 days after treatment has ended

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment sequence T1-T2-R; T1: Lower dose of BI 474121 and higher dose of placebo followed by intravenous ketamine infusion T2: Higher dose of BI 474121 and lower dose of placebo followed by intravenous ketamine infusion R: Lower dose of placebo and higher dose of placebo followed by intravenous ketamine infusion	Drug: Placebo; Placebo; Drug: BI 474121; BI 474121; Drug: Ketamine hydrochloride; Ketamine hydrochloride
Experimental: Treatment sequence T2-T1-R	Drug: Placebo; Placebo; Drug: BI 474121; BI 474121; Drug: Ketamine hydrochloride; Ketamine hydrochloride
Experimental: Treatment sequence T1-R-T2	Drug: Placebo; Placebo; Drug: BI 474121; BI 474121; Drug: Ketamine hydrochloride; Ketamine hydrochloride
Experimental: Treatment sequence T2-R-T1	Drug: Placebo; Placebo; Drug: BI 474121; BI 474121; Drug: Ketamine hydrochloride; Ketamine hydrochloride
Experimental: Treatment sequence R-T1-T2	Drug: Placebo; Placebo; Drug: BI 474121; BI 474121; Drug: Ketamine hydrochloride; Ketamine hydrochloride
Experimental: Treatment sequence R-T2-T1	Drug: Placebo; Placebo; Drug: BI 474121; BI 474121; Drug: Ketamine hydrochloride; Ketamine hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Difference between the total number of errors adjusted for stages that subjects did not complete in the paired associate learning test (PALTEA28), post-ketamine minus the PALTEA28 pre-ketamine	up to 22 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Difference between the between errors in the spatial working memory test (SWMBE468), post-ketamine minus the SWMBE468 pre-ketamine	up to 22 days
Difference between the Rapid Visual Information Processing test A' (RVPA), post-ketamine minus the RVPA pre-ketamine	up to 22 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Anticipated): November 7, 2022
• Primary Completion (Anticipated): June 5, 2023
• Study Completion (Anticipated): June 20, 2023

Study Registration Dates

• First Submitted: July 6, 2022
• First Submitted That Met QC Criteria: July 6, 2022
• First Posted (Actual): July 11, 2022

Study Record Updates

• Last Update Posted (Actual): August 1, 2022
• Last Update Submitted That Met QC Criteria: July 28, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 1411-0003

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. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to:

https://www.mystudywindow.com/msw/datatransparency

Drug and device information, study documents

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