Study of Systemic and Ocular Safety and Pharmacokinetics of BI 409306 in Patients With Schizophrenia, Alzheimer's Disease, and Healthy Volunteers

NCT02392468 | Completed Phase 1 Results

• 1 other identifier: 1289.27
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 3

Brief Summary

Single site, parallel-group, double-blind trial of low or high dose of BI 409306 to evaluate the ocular and systemic safety and pharmacokinetics during 14 day treatment period in patients with schizophrenia, Alzheimer's disease, or age comparable healthy volunteers.

Conditions

Schizophrenia; Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• The Percentage of Participants With Adverse Events (AEs), Coded to the Medical Dictionary for Regulatory Activities - System Organ Class Eye Disorders, as Determined by the Investigator at the End of Trial

  The percentage of participants with Adverse Events (AEs), coded to the Medical Dictionary for Regulatory Activities (MedDRA) - System Organ Class (SOC) 'Eye disorders', as determined by the investigator at the End of Trial (EOT) is reported. Percentages were rounded to one decimal place.

  From the first dose of trial medication until 7 days after last in-take of trial medication, 21 days.

Secondary Outcomes (3)

• The Percentage of Participants With Drug-related AEs as Determined by the Investigator at EOT

  From the first dose of trial medication until 7 days after last in-take of trial medication, 21 days.

• Maximum Measured Concentration of BI 409306 in Plasma at Steady-state (Cmax,ss)

  Pharmacokinetic blood samples were taken at 2:00 (hours: minutes) before and 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 4:00, 6:00 (hours: minutes) after drug administration on day 14.

• Time From Dosing to Maximum Measured Concentration of BI 409306 in Plasma at Steady-state (Tmax,ss)

  Pharmacokinetic blood samples were taken at 2:00 (hours: minutes) before and 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 4:00, 6:00 (hours: minutes) after drug administration on day 14.

Study Arms (6)

BI 409306 25 milligram (mg) - Alzheimer patients

EXPERIMENTAL

Alzheimer patients received once daily (QD) orally one tablet of 25 mg of BI 409306 and two 50 mg matching placebo tablets for 14 days.

Drug: Placebo matching BI 409306 50 mg; Drug: BI 409306 25 mg

BI 409306 100 mg - Alzheimer patients

EXPERIMENTAL

Alzheimer patients received once daily (QD) orally 100 mg of BI 409306 (two 50 mg active tablets) and one 25 mg matching placebo tablet for 14 days.

Drug: Placebo matching BI 409306 25 mg; Drug: BI 409306 50 mg

BI 409306 25 mg - Schizophrenia patients

EXPERIMENTAL

Schizophrenia patients (cognitive impairment associated with schizophrenia) received once daily (QD) orally one tablet of 25 mg of BI 409306 and two 50 mg matching placebo tablets for 14 days.

Drug: Placebo matching BI 409306 50 mg; Drug: BI 409306 25 mg

BI 409306 100 mg - Schizophrenia patients

EXPERIMENTAL

Schizophrenia patients (cognitive impairment associated with schizophrenia) received once daily (QD) orally 100 mg of BI 409306 (two 50 mg active tablets) and one 25 mg matching placebo tablet for 14 days.

Drug: Placebo matching BI 409306 25 mg; Drug: BI 409306 50 mg

BI 409306 25 mg - Healthy volunteers

ACTIVE COMPARATOR

Age-comparable healthy volunteers received once daily (QD) orally one tablet of 25 mg of BI 409306 and two 50 mg matching placebo tablets for 14 days.

Drug: Placebo matching BI 409306 50 mg; Drug: BI 409306 25 mg

BI 409306 100 mg - Healthy volunteers

ACTIVE COMPARATOR

Age-comparable healthy volunteers received once daily (QD) 100 mg of BI 409306 (two 50 mg active tablets) and one 25 mg matching placebo tablet orally for 14 days.

Drug: Placebo matching BI 409306 25 mg; Drug: BI 409306 50 mg

Interventions

Placebo matching BI 409306 25 mg DRUG

Film-coated tablet

BI 409306 100 mg - Alzheimer patients; BI 409306 100 mg - Healthy volunteers; BI 409306 100 mg - Schizophrenia patients

Placebo matching BI 409306 50 mg DRUG

Film-coated tablet

BI 409306 25 mg - Healthy volunteers; BI 409306 25 mg - Schizophrenia patients; BI 409306 25 milligram (mg) - Alzheimer patients

BI 409306 25 mg DRUG

Film-coated tablet

BI 409306 25 mg - Healthy volunteers; BI 409306 25 mg - Schizophrenia patients; BI 409306 25 milligram (mg) - Alzheimer patients

BI 409306 50 mg DRUG

Film-coated tablet

BI 409306 100 mg - Alzheimer patients; BI 409306 100 mg - Healthy volunteers; BI 409306 100 mg - Schizophrenia patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Schizophrenia group:
• Patients with established diagnoses of schizophrenia (per Diagnostic and Statistic Manual of Mental Disorder, version V) with the all of the following clinical features:
• Clinically stable and are in the residual (non-acute) phase of their illness for at least 8 weeks prior to randomisation
• Current antipsychotic and concomitant psychotropic medications must meet the criteria below:
• Maintained on current atypical (second generation) antipsychotic medications (in any approved dosage form) other than Clozapine and on current dose for at least 8 weeks prior to randomisation, and/or
• Maintained on current typical (first generation) antipsychotic medications and on current dose for at least 6 months, optionally combined with anticholinergics if treated with a stable dose for at least 6 months prior to randomisation, and/or
• Maintained on current concomitant psychotropic medications other than anticholinergics, antiepileptics and lithium, and on current dose for at least 8 weeks prior to randomisation. Antiepileptics and lithium are allowed if initiated at least 6 months prior to randomisation.
• Have no more than a moderate severity rating on hallucinations and delusions (Positive and Negative Syndrome Scale (PANSS), positive syndrome Hallucinatory Behavior item score \<= 4 and Delusions item score \<= 4)
• Have no more than a moderate severity rating on positive formal thought disorder (PANSS, positive syndrome Conceptual Disorganization item score \<= 4)
• Have a minimal level of extrapyramidal symptoms (Simpson-Angus Scale total score \< 6) and depressive symptoms (PANSS, general psychopathology syndrome Depression item score \<= 4)
• Male or female patients age 18 to 55 years.
• Alzheimer's Disease group:
• Patients with diagnosis of mild Alzheimer's Dementia based on DSM-V and in accordance with the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease.
• Mini-Mental State Examination (MMSE) score of 18-26.
• Male or female patients age 55 to 85 years, who have not been taking acetyl cholinesterase inhibitors (donepezil, galantamine, rivastigmine) and/or memantine for at least 3 months or on stable dose of acetyl cholinesterase inhibitors (donepezil, galantamine, rivastigmine) and/or memantine at least 3 months before randomization.Patients older than 85 years may be included based on an acceptable general health status, (e.g. concomitant diseases, physical capability to follow the required study procedures \[visits etc.\]) per investigators judgement.

You may not qualify if:

• If needed, a caregiver may be present during site activities.
• Age-comparable male or female healthy volunteers age 18 to 85 years. Healthy volunteers older than 85 years may be included based on an acceptable general health status, (e.g. concomitant diseases, physical capability to follow the required study procedures \[visits etc.\]) per investigators judgement:
• After 10 patients with schizophrenia (as described above) are entered into the study, the median age of the group will be computed. Five healthy volunteers at or below the median age but greater than 18 years old and five healthy volunteers above the median but less than 55 will be entered into the study.
• Similarly, after 10 patients with AD are entered, the median age will be computed. Five healthy volunteers at or below the median age but greater than 55 years old and five healthy volunteers above the median but less than 85 will be entered into the study.
• Subjects must exhibit reliability and physiologic capability to comply with all protocol procedures.
• Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice and the local legislation. If the patient needs a legal representative, then this legal representative must give written informed consent as well.
• Presence of active ocular conditions with or without visual impairment due to any causes (e.g. cataract, chorioretinal macular lesion, amblyopia, active diabetic retinopathy, uncontrolled glaucoma, active inflammation or infection, etc.) in one eye or both eyes at the screening phase.
• Planned ocular treatment (e.g. intravitreal antivascular growth factor, corticosteroids) or surgery during the study period.
• Current or planned use of ocular or systemic corticosteroids.
• Current or planned use of medications known to be toxic to the retina, lens, optic nerve
• Subjects treated with more than two antipsychotic medications (including more than two dosage forms).
• Dementia in Alzheimers Disease patients, secondary to other disorders (based on clinical data and/or current laboratory findings and/or on a pre-existing cranial MRI or CCT).
• Neurological disease (other than Dementia of Alzheimer Type such as: Lewy body dementia - primary diagnosis, Huntington's disease, Parkinson's Disease encephalitis, epilepsy, vascular or multi-infarct dementia, stroke, congenital mental deficiency, or multiple sclerosis), or mental retardation.
• Subjects needing to take long-acting hypnotics or anxiolytic (i.e. Diazepam).
• For AD patients, the following drugs are prohibited for 3 months prior to randomization and for the duration of the trial:

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (3)

University of California San Diego

La Jolla, California, 92037, United States

Location

Memory Enhancement Center of America, Inc.

Eatontown, New Jersey, 07724, United States

Location

Community Clinical Research, Inc.

Austin, Texas, 78754, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Schizophrenia; Alzheimer Disease

Interventions

BI 409306

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2015
• First Posted: March 19, 2015
• Study Start: April 15, 2015
• Primary Completion: August 3, 2017
• Study Completion: August 10, 2017
• Last Updated: April 19, 2024
• Results First Posted: April 19, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Locations

US (3)