Depressive DisorderPhase 1NCT00511654
28-day Repeat Dose and Drug Interaction Study With Orvepitant (GW823296)
A Phase 1 study testing GW823296 tablet and Midazolam in people with Depressive Disorder, run by GlaxoSmithKline at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Depressive Disorder
- What is being tested?
- GW823296 tablet and Midazolam
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteGermany
- Study dates
- 12 Jun 2007to 11 Jan 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
- Subjects with a history of myopathy or rhabdomyolysis
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- The subject is unable to abstain from strenuous physical activity for 72 hours prior to screening, for 72 hours prior first dosing until the last PK sample has been collected, and for 72 hours prior to the follow-up visit.
- The subject has donated a unit of blood (450 mL) within the previous 60 days or intends to donate in the month after completing the study.
- The subjects is currently taking regular (or a course of) medication whether prescribed or not, including vitamins and herbal remedies, such as St John's Wort. Any concurrent medication will not be permitted for 48 hours before admission to the CPRU until the end of the study period (follow-up visit).
- Typical consumption of more than 14 alcoholic units in any week, or more than 3 (for males) or 2 (for females) alcoholic units in any single day, over the month preceding the screening visit [NOTE: 1 unit = 8 oz beer, 3 oz wine, or 1 oz hard liquor]
- The subject smokes or has smoked in the last 3 months.
- The subject has tested positive for Hepatitis C antibody or Hepatitis B surface antigen.
- The subject has tested positive for HIV-1/2.
- The subject has a past history of drug abuse or has tested positive for urine drugs of abuse at screening. A minimum list of drugs that will be screened for include Amphetamines, Barbiturates, Cocaine, Opiates, Cannabinoids and Benzodiazepines.
- Male subject intends to father a child during the study and the 3 months following the study
- Subjects with a history of eye disease (excluding moderate myopia) or clinically relevant eye examination finding, which in the opinion of the study ophthalmologist contraindicates their participation in the study
- Vulnerable subject (e.g. kept in detention)
- Subjects who have had hypersensitivity or intolerance to NK1 antagonists
- Subject has a known hypersensitivity against midazolam or against one of the excipients of Dormicum® (subjects of Cohorts 2 and 3 only)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Parallel Group, Single-Blind, Randomised, Placebo Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GW823296 and Its Effect on the Pharmacokinetics of Midazolam After Once-Daily Repeated Oral Doses in Healthy Subjects
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
- Being tested
- GW823296 tablet, GW823296 matching placebo, Midazolam
- Keywords
- depression, NK1 receptor antagonists,
- Medical subject headings
- Depressive Disorder, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GW823296 tabletDrug
Also called Orvepitant
GW823296 immediate release tablets will be available as white film-coated tablets containing 5 milligrams (mg) and 20 mg of GW823296 for oral administration.
GW823296 matching placeboDrug
Matching placebo tablets will be identical in appearance to the GW823296 tablets.
MidazolamDrug
Midazolam will be administered as 5 milliliter (mL) of an intravenous solution for oral application (5 mg/5 mL, Dormicum).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: GW823296 matching placebo; Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety and tolerability of oral doses of GW823296 given once daily for 28 days in healthy male and female subjects
Measured: 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.
Measured: 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)
Measured: 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
Measured: Up to Day 30
Effect of repeated daily oral doses of GW823296 on urine 6-b-hydroxycortisol / cortisol ratio
Measured: Up to Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2007 (estimated)
- Study start12 Jun 2007
- Primary completion11 Jan 2008
- Study completion11 Jan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depressive DisorderStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00511654
- Sponsor's protocol ID
- NKG10004
- Status last verified
- Aug 2017
- First submitted
- 2 Aug 2007
- Last updated
- 4 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Parallel Group, Single-Blind, Randomised, Placebo Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GW823296 and Its Effect on the Pharmacokinetics of Midazolam After Once-Daily Repeated Oral Doses in Healthy Subjects
- ClinicalTrials.gov ID
- NCT00511654
- Acronym / sponsor ID
- NKG10004
- Conditions
- Depressive Disorder
- Keywords
- depression, NK1 receptor antagonists,
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 12 Jun 2007 (actual)
- Primary completion
- 11 Jan 2008 (actual)
- Study completion
- 11 Jan 2008 (actual)
- First posted
- 6 Aug 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Subjects in Group 1 receiving GW823296 | Experimental | Drug: GW823296 tabletSubjects 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. |
| Subjects in Group 1 receiving placebo | Placebo comparator | Drug: GW823296 matching placeboSubjects 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. |
| Subjects in Group 2 and 3 receiving GW823296 | Experimental | Drug: GW823296 tablet, Drug: MidazolamSubjects 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. |
| Subjects in Group 2 and 3 receiving placebo | Placebo comparator | Drug: GW823296 matching placebo, Drug: MidazolamSubjects 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GW823296 tabletAlso: OrvepitantGW823296 immediate release tablets will be available as white film-coated tablets containing 5 milligrams (mg) and 20 mg of GW823296 for oral administration. | Drug | Subjects in Group 1 receiving GW823296, Subjects in Group 2 and 3 receiving GW823296 |
| GW823296 matching placeboMatching placebo tablets will be identical in appearance to the GW823296 tablets. | Drug | Subjects in Group 1 receiving placebo, Subjects in Group 2 and 3 receiving placebo |
| MidazolamMidazolam will be administered as 5 milliliter (mL) of an intravenous solution for oral application (5 mg/5 mL, Dormicum). | Drug | Subjects in Group 2 and 3 receiving GW823296, Subjects in Group 2 and 3 receiving placebo |
Primary outcome
To assess the safety and tolerability of oral doses of GW823296 given once daily for 28 days in healthy male and female subjects
Time frame: Up to Day 43
4 secondary outcomes
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.
Time frame: 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)
Time frame: 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
Time frame: Up to Day 30
Effect of repeated daily oral doses of GW823296 on urine 6-b-hydroxycortisol / cortisol ratio
Time frame: Up to Day 30
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2017.
- Results for study NKG10004 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GW823296 tablet and Midazolam in people with Depressive Disorder, run by GlaxoSmithKline at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the safety and tolerability of oral doses of GW823296 given once daily for 28 days in healthy male and female subjects (time frame: Up to Day 43). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2017; AzTrials last refreshed its copy on 30 Oct 2026.