28-day Repeat Dose and Drug Interaction Study With Orvepitant (GW823296)

NCT00511654 | Completed Phase 1

• 1 other identifier: NKG10004
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Depressive Disorder

Keywords

depression; NK1 receptor antagonists,

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

Study Arms (4)

Subjects in Group 1 receiving GW823296

EXPERIMENTAL

Subjects will receive single dose of GW823296 on Day 1 followed by a wash-out period of 1 week. The subjects will then be administered GW823296 for 28 days in the repeat dosing period.

Drug: GW823296 tablet

Subjects in Group 1 receiving placebo

PLACEBO COMPARATOR

Subjects will receive single dose of placebo on Day 1 followed by a wash-out period of 1 week. The subjects will then be administered placebo for 28 days in the repeat dosing period.

Drug: GW823296 matching placebo

Subjects in Group 2 and 3 receiving GW823296

EXPERIMENTAL

Subjects will receive single dose of midazolam on Day 1 followed by wash-out period of one day. Further the subjects will be administered GW823296 on Day 3 of single dose period followed by a wash-out period of 1 week. The subjects will then be administered a single dose of GW823296 for 28 days (Day 1 to Day 28 of repeat dosing period) and a single dose of midazolam on Day 29 of repeat dosing period.

Drug: GW823296 tablet; Drug: Midazolam

Subjects in Group 2 and 3 receiving placebo

PLACEBO COMPARATOR

Subjects will receive single dose of midazolam on Day 1 followed by wash-out period of one day. Further the subjects will be administered placebo on Day 3 of single dose period followed by a wash-out period of 1 week. The subjects will then be administered a single dose of placebo for 28 days (Day 1 to Day 28 of repeat dosing period) and a single dose of midazolam on Day 29 of repeat dosing period.

Drug: GW823296 matching placebo; Drug: Midazolam

Interventions

GW823296 tablet DRUG

GW823296 immediate release tablets will be available as white film-coated tablets containing 5 milligrams (mg) and 20 mg of GW823296 for oral administration.

Also known as: Orvepitant

Subjects in Group 1 receiving GW823296; Subjects in Group 2 and 3 receiving GW823296

GW823296 matching placebo DRUG

Matching placebo tablets will be identical in appearance to the GW823296 tablets.

Subjects in Group 1 receiving placebo; Subjects in Group 2 and 3 receiving placebo

Midazolam DRUG

Midazolam will be administered as 5 milliliter (mL) of an intravenous solution for oral application (5 mg/5 mL, Dormicum).

Subjects in Group 2 and 3 receiving GW823296; Subjects in Group 2 and 3 receiving placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• 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.
• The subject has screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>1.5x upper limit of the normal range (ULN); testing may be repeated once to see if value returns to within acceptance range but any such laboratory abnormality must be resolved by the baseline visit.
• Subjects with a troponin I value \>0.032 ng/mL at screening are not eligible. Testing may not be repeated. The subject should be referred to the treating physician for further evaluation, as appropriate.
• Subjects with a TSH value above the upper limit of the normal range (ULN) at screening are not eligible. The subject should be referred to the treating physician for further evaluation, as appropriate. Testing may be repeated once to see whether the value returns to within normal range but such abnormality must be resolved before the baseline visit.
• Subjects found to have stool positive for occult blood. If such a stool was obtained without the subject abstaining from red meat for 3 or more days prior to testing, this may be repeated once following such abstinence. If that stool is negative for occult blood the subject is considered eligible.
• Subjects with known or suspected iron deficiency

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Berlin, 14050, Germany

Location

Related Links

• Results for study NKG10004 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Depressive Disorder; Depression

Interventions

orvepitant; Midazolam

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 2, 2007
• First Posted: August 6, 2007
• Study Start: June 12, 2007
• Primary Completion: January 11, 2008
• Study Completion: January 11, 2008
• Last Updated: August 4, 2017

Record last verified: 2017-08

Locations

DE (1)