anxiety disorder Panic disorder
Conditions
Interventions
GRX-917
Alprazolam
Sponsors
GABA Therapeutics Australia Pty. Ltd.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Healthy male and female subjects ages 18 to 55 years (Part 1) and 45 to 65 years (Part 2), inclusive, at the time of signing the ICF. - (Part 1 only): Defined as sensitive to the anxiogenic effects of double-breath CO2 inhalation as defined in the protocol. - A female subject of childbearing potential who is sexually active with a non-sterilized male partner must agree to use double highly effective method of contraception from signing of informed consent and for 90 days post last dose. A male subject with a pregnant or a nonpregnant partner of childbearing potential must agree to also use double highly effective method of contraception (i.e., condom or abstinence) during treatment and until the end of relevant systemic exposure in the male subject for 90 days following the last dose.
Exclusion criteria
Exclusion criteria: - Subjects with a current history of clinically significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, haematological, immunological, or neurological disease that, in the opinion of the investigator or medical monitor, could compromise either subject safety or the results of the trial. - (Part 1 only): Subjects with a current or past history of clinically significant respiratory conditions, including asthma, lung fibrosis, and non-invalidating chronic obstructive pulmonary disease. - Subjects with a clinically significant current or past personal or family history of any psychiatric disorder as classified by DSM-4 or DSM-5 criteria. - Subjects with epilepsy. - (Part 2 only): Females with irregular cycles or females with regular cycles of more than 35 days - Subject has a history of malignancy within 5 years before screening. - Use or intend to use any medications/products which are known moderate or strong inhibitors or inducers of the CYP2B6, CYP3A4, CYP2C19 or CYP2D6 enzymes for 28 days prior to Check-in on Day 1 and throughout the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1: • Difference in mean change from baseline in the PSL-IV total score from pre-CO2 to post-CO2 challenge Part 2: • Geometric mean accumulation ratios (Day 27 vs. Day 1) for GRX-917 and major metabolite (M4) for Cmax and AUC0-24 in plasma. • GRX-917 and major metabolite, M4, concentrations by dose and time point. CSF PK parameters to be assessed include Tmax, Cmax, Cmin, AUC0-t, AUC0-24, AUC0-inf, t*, CSF/plasma and metabolite-parent ratios. | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 1 and 2 • Difference in mean change in VAS Fear score from pre-CO2 to post-CO2 challenge • Difference in mean change from pre-CO2 to post-CO2 challenge in vital sign measurements (systolic blood pressure, diastolic blood pressure, heart rate) related to the cardiovascular response to CO2 inhalation challenge using Finapres Assessments • GRX 917 and major metabolite, M4 plasma concentrations • NeuroCart assessments: o Absolute measurements and change from baseline of saccadic eye movements (saccadic reaction time, saccadic peak velocity [deg/sec], and saccadic inaccuracy) o Absolute and change from baseline body sway (antero-posterior sway [mm/2 minutes]) o Absolute and change from baseline of adaptive tracking (%) o Absolute and change from baseline of Bond & Lader VAS (alertness, calmness, mood subscales [mm]) • Absolute and change from baseline of Quantitative electroencephalograms (qEEG) (eyes open-eyes closed) • Treatment-emergent AEs, clinically significant changes in Electrocardiogram (ECG) parameters, clinical laboratory assessments, vital sign measurements, physical and neurological examination results, and suicidality as assessed by C-SSRS | — |
Countries
Netherlands
Outcome results
None listed