Last updated: 08/13/2019 19:20:17
Effects of SB-649868 and Alprazolam on the Neuroendocrine and Sympathetic Responses to Insulin-Induced Hypoglycaemia in Healthy Male Subjects
Clinicaltrials.gov ID
Not applicable
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: Effects of SB-649868 and Alprazolam on the Neuroendocrine and Sympathetic Responses to Insulin-Induced Hypoglycaemia in Healthy Male Subjects
Trial description: SB-649868 is an orally active orexin 1 and orexin 2 (OxR1/OxR2) receptor antagonistthat has been developed as a treatment for primary insomnia. As detailed below, it hassleep-inducing effects at doses of 10 mg or greater. However, its pharmacodynamics atlower doses have not been as extensively investigated. It has also not previously beenstudied under experimental conditions likely to be associated with high levels ofendogenous orexin release. Demonstration of low dose pharmacological effects of SB-649868 could encourage further clinical development of orexin antagonists for hyperarousalsyndromes, such as alcohol withdrawal, panic disorder or post-traumatic stressdisorder.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Single (Participant)
Allocation:
Randomized
Primary outcomes:
To test the hypothesis that SB-649868, administered at doses of 10 mg or less reduces activation of the HPA-axis in response to insulin-induced hypoglycaemia
Timeframe: At 11 intervals from 30 minutes pre-dose to 210 minutes post dose at all 3 sessions
To test the hypothesis that SB-649868, administered at doses of 10 mg or less, reduces activation of the sympathetic nervous system in response to insulin-induced hypoclycaemia
Timeframe: Continuous monitoring at all 3 sessions between 60 minutes pre-dose and 270 minutes post-dose
Secondary outcomes:
To investigate the effects of SB-649868 on mood and behavioural responses to insulin-induced hypoglycaemia
Timeframe: Performed at all 3 sessions, one day prior to dosing and performed at multiple times from 30 minutes pre-dose to 210 minutes post-dose depending on the endpoint.
Interventions:
Drug: sb-649868
Drug: alprazolam
Enrollment:
36
Observational study model:
Cohort
Primary completion date:
2012-09-04
Time perspective:
Prospective
Clinical publications:
Ameera Patel, Sam Miller, Pradeep Nathan, Ponmani Kanakaraj, Antonella Napolitano, Phil Lawrence, Annelize Koch, Edward Bullmore . Neuroendocrine and sympathetic responses to an orexin receptor antagonist, SB-649868, and Alprazolam following insulin-induced hypoglycaemia in humans. Psychopharmacology (Berl). 2014;231(19):3817–3828
Medical condition
Anxiety Disorders
Product
SB649868
Collaborators
Not applicable
Study date(s)
June 2011 to April 2012
Type
Interventional
Phase
1
Participation criteria
Sex
Male
Age
18 - 45 Year
Accepts healthy volunteers
yes
- 1. Subject is a healthy male adult subject aged 18 to 45 years, inclusive.
- 2. BMI within the range 19.0 to 25.9 kg/m2
- 1. The subject has either a previous disease or current medical condition, which as
- judged by the Investigator, may compromise safety or affect the interpretation of
Inclusion and exclusion criteria
Inclusion criteria:
- 1. Subject is a healthy male adult subject aged 18 to 45 years, inclusive. 2. BMI within the range 19.0 to 25.9 kg/m2 3. Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, psychiatric history, psychiatric evaluation, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to compromise subject safety or interfere with study integrity. 4. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Exclusion criteria:
- 1. The subject has either a previous disease or current medical condition, which as judged by the Investigator, may compromise safety or affect the interpretation of efficacy data. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematological disease, gastro-intestinal disease, neurological disease, psychiatric diseases, immunological disease or endocrine disease, including autonomic diseases eg. hyperhidrosis/anhidrosis as we are measuring sudomotor function with GSR. 39 2. The subject has a history of hypopituitarism and/or hypoadrenalism and/or morning plasma cortisol < 100 nmol/L at screening; ischaemic heart disease or other cardiac disease; type 1 or type 2 diabetes and/or fasting plasma glucose > 6.0mmol/L at screening; hypothyroidism or hyperthyroidism; epilepsy or any episodes of disturbed consciousness. 3. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. 4. Current history of depression (self-administered Beck Depression Inventory II scale total score greater than 13 at screening). 5. Fasting plasma insulin greater than 60pmol/L at screening. 6. Systolic blood pressure (BP) below 90 or > 140mm Hg, or diastolic blood pressure (BP) below 50 or above 90 mmHg. 7. Abnormalities in 12-lead ECG at screening that indicate arrhythmia, ischaemic heart disease or any other cardiac condition considered clinically significant by the Investigator or Medical Monitor; 8. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety 9. The subject has a history of alcohol or substance abuse or dependence in the 6 months prior to screening as determined by the investigator. Abuse of alcohol, defined for males, as an average weekly intake of greater than 21 units (or an average daily intake of greater than 3 units), or defined for females, as an average weekly intake of greater than 14 units (or an average daily intake of greater than 2 units). One unit is equivalent to a half-pint (220mL) of beer or 1 (25mL) measure of spirits or 1 glass (125mL) of wine. 10. Subjects will be excluded if they have a history of adverse reactions to, or dependence on, benzodiazepines, and will be continuously monitored after dosing on study assessment days. 11. Subjects who use tobacco products will be instructed to smoke less than 10 a day during the study and they will not be allowed to smoke or use nicotine containing products during the study visit days (see Section 8.3.). 12. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 3 months before or after the study. 13. The subject has a positive urine drug test at screening or when tested at any of the study visits. 14. Subjects with plasma cTpn I values above the 99th percentile of normal range of the selected assay 15. 15. AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). 16. Subject who, in the investigator/designee's judgement, poses a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behaviour and/or any evidence of suicidal ideation on any questionnaires e.g. type 4 or 5 on the C-SSRS in the last 6 months. 17. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the dosing day in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). 18. A subject with known long term hearing impairment or who reports impaired hearing at the telephone screening.
Trial location(s)
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Completed
Actual primary completion date
2012-09-04
Actual study completion date
2012-09-04
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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