Depressive Disorder
Conditions
Keywords
depression, NK1 receptor antagonists,
Brief summary
This study is being conducted to obtain information on the safety and tolerability of repeated doses of GW823296 for 28 days in healthy male and female subjects. In addition, the pharmacokinetics of GW823296 will be evaluated to confirm the doses to be used in Phase II efficacy studies. The effect of repeat dose (RD) of GW823296 on CYP3A4 enzyme activity will be investigated evaluating the pharmacokinetics of midazolam and urine 6-?-hydroxycortisol/cortisol ratio.
Interventions
DRUGGW823296 tablet
GW823296 immediate release tablets will be available as white film-coated tablets containing 5 milligrams (mg) and 20 mg of GW823296 for oral administration.
DRUGGW823296 matching placebo
Matching placebo tablets will be identical in appearance to the GW823296 tablets.
DRUGMidazolam
Midazolam will be administered as 5 milliliter (mL) of an intravenous solution for oral application (5 mg/5 mL, Dormicum).
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy as determined by a Physician Responsible, based on a medical evaluation including history, physical examination, laboratory tests, cardiac monitoring. A subject with a clinical abnormality or laboratory variables outside the reference range for the population being studied, with the exception of liver transaminases, troponin I and TSH, may be included only if the Investigator considers that the finding will not introduce additional risk factors and will not interfere with the study procedures. Please note that subjects should have liver transaminases, troponin I and TSH values within the range specified in the
Exclusion criteria
below. * Women of non-childbearing potential (i.e., physiologically incapable of becoming pregnant with documentation of hysterectomy or bilateral ovariectomy \>6 months, including any female who is postmenopausal. For purposes of this study, postmenopausal is defined as one year without menses and confirmed by FSH according to the local laboratory ranges at screening) and having a negative serum hCG pregnancy test at screening. * No co-morbid Psychiatric Disorders as defined using the Mini International Neuropsychiatric Interview (M.I.N.I) scale * Aged 18-65 years, inclusive * A 12-lead ECG and 24-hours Holter ECG at screening showed no abnormalities that in the opinion of the Principal Investigator will compromise safety in this study * Body weight \>50 kg and body mass index (BMI) within the range 19.0-29.9 kg/m2 * Subjects with a history of peptic ulcer disease (PUD) with a known aetiology must provide documentation by a gastroenterologist of the aetiology of the PUD and that effective treatment was provided with full eradication of ulcers and symptoms. For such subjects appropriate steps must also have been taken to minimize reoccurrence risk (i.e. if PUD was nonsteroidal anti-inflammatory drug \[NSAID\] induced, the subject should no longer be taking NSAID medications; if cause was Helicobacter pylori \[H. pylori\], the subject should have been appropriately treated). For all subjects, regardless of whether there is a positive history of PUD, sites are required to document their H. pylori status at screening. Entry into the study is permitted for subjects who are seropositive for H. pylori, but treatment is recommended, either before or after study participation at the discretion of the Principal Investigator. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form * The subject must be able to read, comprehend and record information. * A signed and dated written informed consent is obtained from the subject. * The subject is available to complete the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the safety and tolerability of oral doses of GW823296 given once daily for 28 days in healthy male and female subjects | Up to Day 43 |
Secondary
| Measure | Time frame |
|---|---|
| To assess the PK of single oral doses of GW823296 given once daily for 28 days and its potential to alter the CYP3A4 enzyme activity in healthy male and female subjects. Pharmacogenetics. | Up to Day 31 |
| PK parameters of GW823296 following repeated oral doses of the GW823296 given once daily: Cmax, tmax, AUC0-τ, accumulation ratio (Ro) and, if possible, lz, t1/2,z, and time invariance (Rs) | Up to Day 31 |
| Effect of repeated daily oral doses of GW823296 on the PK of single doses of midazolam: Cmax, tmax, AUC0-t, and, if possible, AUC0-∞ and lz and t1/2,z of midazolam | Up to Day 30 |
| Effect of repeated daily oral doses of GW823296 on urine 6-b-hydroxycortisol / cortisol ratio | Up to Day 30 |
Countries
Germany
Outcome results
None listed