Neurological disorders
Conditions
Interventions
One single oral dose of each of the following treatments is administered per treatment period:Alprazolam, 2 x 0.5 mg over-encapsulated tablets, with one placebo capsule 
Modafinil, 3 x 200 mg over-encapsulated tablets, without placebo capsules 
Three placebo capsules
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Signed informed consent prior to any study-mandated procedure. 2. Healthy males or healthy postmenopausal females, 18 to 55 years of age, inclusive at screening. 3. Body mass index (BMI) between 18 and 32 kg/m2, inclusive at screening, and with a minimum weight of 50 kg. 4. Males who are sexually active and whose partners are women of childbearing potential (WOCBP) must agree to use condoms from screening through at least 7 days after administration of the last dose of IMP, or their partners must be willing to use a highly effective method of contraception (e.g. intrauterine device [IUD], diaphragm with spermicide, oral contraceptive, injectable progesterone, subdermal implant, or tubal ligation). Other effective male contraception also includes a vasectomy with negative semen analysis at follow up. Abstinence can be considered an acceptable method of contraception at the discretion of the investigator. Males must also agree not to donate sperm through 7 days after administration of the last dose of IMP. For females, follicle-stimulating hormone (FSH) levels will be determined during screening to confirm postmenopausal status. 5. Has the ability to communicate well with the Investigator in the Dutch language and willing to comply with the study restrictions.
Exclusion criteria
Exclusion criteria: 1. Evidence of any active or chronic disease or condition that could interfere with, or for which the treatment might interfere with the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator (following a detailed medical history, physical and neurological examination, vital signs (systolic and diastolic blood pressure, pulse rate, body temperature) and 12-lead ECG). Minor deviations from the normal range may be accepted, if judged by the Investigator to have no clinical relevance. 2. Clinically significant abnormalities, as judged by the investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy study participants. 3. History or presence of conditions which, in the judgment of the investigator, might increase the risk of performing TMS, including but not limited to epilepsy or febrile seizures, intracranial mass lesion, hydrocephalus, clinically significant head injury or trauma, metal objects in the brain or skull, cochlear implant or a deep brain stimulation device. 4. Personal or relevant family history of psychiatric diseases, including but not limited to bipolar disorder and anxiety disorder. 5. Any condition that could interfere with the quality of, or ability to perform, TMS, such as an abnormal sleeping pattern (e.g., working night shifts), dreadlocks or hairpieces that cannot be removed, or a resting motor threshold (rMT) of more than 62% of the maximum stimulator output as measured using TMS-EMG during screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate the pharmacodynamic (PD) effects of modafinil and alprazolam in healthy male and female postmenopausal adults when compared to placebo on: Cortical excitability as measured by single-pulse TMS-EMG motor evoked potential (MEP) amplitude Brain E/I ratio using the Mean Field Model (MFM) and 1/f parameters from raw qEEG data. | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the PD effects of modafinil and alprazolam on cortical excitability as measured by single- and paired-pulse TMS-EMG in healthy male and female postmenopausal adults when compared to placebo.To evaluate the PD effects of modafinil and alprazolam on cortical excitability as measured by single- and paired-pulse TMS-EEG in healthy male and female postmenopausal adults when compared to placebo. To evaluate the PD effects of modafinil and alprazolam on qEEG spectral power in healthy male and female postmenopausal adults when compared to placebo. CHDR2431 Protocol Version 1 / 15-Apr-2025 Confidential Page 14 of 54To evaluate the brain excitation/inhibition ratio using the Mean Field Model (MFM) and 1/f parameters from raw qEEG data. | — |
Countries
Netherlands
Contacts
Public ContactG.J. Groeneveld
Centre for Human Drug Research
Outcome results
None listed