| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To compare the efficacy of GW679769 with placebo on night-time sleep parameters when GW679769 is acutely and repeatedly administered in the morning to subjects with Primary Insomnia as determined objectively by polysomnography (PSG). |
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| E.2.2 | Secondary objectives of the trial |
•To compare the efficacy of GW679769 and placebo acutely and repeatedly administered in the morning on subjective measures of sleep onset, continuity, duration and quality using self reported Post-Sleep Questionnaires administered by an Interactive Voice Response System (IVRS)
•To compare the effects of GW679769 and placebo acutely and repeatedly administered in the morning on cognitive functioning; attention and alertness.
•To evaluate the safety and tolerability of GW679769 compared with placebo.
•To evaluate the PK-pharmacodynamic (PD) relationship between GW679769 exposure and efficacy, safety, and tolerability.
•To potentially investigate changes in transcriptomic profiles of peripheral whole blood (PAXgene), and of proteomic profiles of plasma, following exposure to GW679769 and placebo to establish relationships between profile changes and improvement of insomnia.
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Able to read and understand the informed consent form and provide written informed consent, indicating understanding of the purpose of the study and willingness to comply with all study procedures described in the protocol, including all sleep-laboratory restrictions and procedures.
2. Male or female between the ages of 18 and 64 years (inclusive).
3. Has a principal diagnosis of primary insomnia, based on Diagnostic and Statistical Manual of Mental Disorders-Text Revision (DSM-IV-TR) criteria 307.42: (please refer to protocol).
4. The self-reported sleep history over the preceding three months indicates:
• a usual total sleep time (TST) of less than six hours, sleep onset latency (SOL) of at least 30 minutes and at least two awakenings per night in at least three nights per week.
• a time in bed between 6.5 and 8.5 hours for at least five nights per week .
• bed time between 21.00 and 24.00 hours that does not vary by more than ±2 hour. Bedtime (lights out) will be confirmed by a one week diary completed before the first polysomnography (PSG) screening session.
5. The sleep variables obtained from the two Screening PSGs (with single-blinded placebo administration each morning) must fall within the protocol-defined ranges.
6. Women of childbearing potential must commit to consistent and correct use of an acceptable method of birth control; GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of a physician, are as follows:
1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal. For purposes of this study, postmenopausal is defined as one year without menses)
2. Child-bearing potential, has a negative serum pregnancy test result at the Screening Visit and negative urine dipstick pregnancy tests at the screening PSG session (Visit 2) and prior to randomization at Visit 4, and agrees to one of the following:
• Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject
• Oral contraceptives (either combined or progestogen only) with double barrier method of contraception consisting of spermicide with either condom or diaphragm throughout the clinical trial, and for six weeks following the last dose of study medication.
• Double-barrier method of contraception consisting of spermicide with either condom or diaphragm
• IUD with a documented failure rate of less than 1% per year
• Complete abstinence from intercourse for two weeks before exposure to the study drug, throughout the clinical trial, and for a period after the trial to account for elimination of the drug (minimum of three days, equivalent to five half lives).
- If subjects indicate they will remain abstinent during the period described above, they must agree to follow GSK guidelines for the consistent and correct use of an acceptable method of birth control should they become sexually active.
7. Is in good health as determined by medical and psychiatric history, physical examination, ECG, and serum chemistry, hematology, serology, and urinalysis results.
8. Subjects with a history of peptic ulcer disease (PUD) with a known etiology must provide documentation by a gastroenterologist of the etiology 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 Heliobacter (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.
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| E.4 | Principal exclusion criteria |
1. Symptoms/signs that are consistent with any primary sleep disorder other than primary insomnia. 2. Any clinically significant psychiatric disorder other than primary insomnia as defined by DSM-IV-TR. 3. A recent history (12 months) of mood of other mental disorders that the investigator regards as accounting for the insomnia.
4. A Beck Depression Inventory (version II) total score of 29 or greater. Subjects scoring 17 to 28 must be confirmed to not have major depressive illness.
5. History of alcohol, narcotic, benzodiazepine, or other substance abuse or dependence (with the exception of tobacco) within 12 months as defined by DSM-IV-TR. 6. Positive urine drug screen at Screening Visit. 7. Alcohol breath test positive for the ingestion of alcohol at the Screening Visit. 8. Any history of a clinically significant abnormality of the neurological system (including dementia and other cognitive disorders or significant head injury) or any history of seizure (including febrile seizure). 9. An unstable medical disorder or a disorder that would likely interfere with the ADME of GW679769, may pose a safety concern or interfere with accurate assessment of efficacy and safety. 10. Has active peptic ulcer disease (PUD) and/or history of PUD of an unknown etiology. 11. Likely to require the use of the following medications: • NSAIDs: use of an NSAID (this includes aspirin) is only permitted when administered concomitantly with an anti-secretory agent i.e., proton-pump inhibitor or histamine-2 receptor antagonist. • concomitant use of aspirin at any dose and NSAIDS including COX2 inhibitors. 12. Has a stool positive for occult blood. If such a stool was obtained without the subject abstaining from red meat for three or more days prior, testing may be repeated once following such abstinence.
13. Has a history of myopathy or rhabdomyolysis. 14. Any serious medical disorder or condition that would in the Investigator's opinion, preclude the administration of study medication. 15. Has any screening electrocardiography (ECG) parameter outside of the Sponsor-specified ranges as determined by a central ECG reader; the ECG may be repeated once to see if the parameter returns to within range but any such abnormality must be resolved by the first day of the screening PSG session.
16. Has any ECG finding that in the investigator's judgement is considered to be clinically significant and not resolved by the first day of the screening PSG session .
17. Known seropositivity for human immunodeficiency virus (HIV), or active Hepatitis B, or Hepatitis C infection. 18. Women having a positive serum HCG pregnancy test at Screening Visit, a positive urine pregnancy dipstick during the screening PSG Session or at randomization, or who are lactating or planning to become pregnant within the three months following the Screening Visit. 19. Has any laboratory value outside of the Sponsor-specified ranges at the Screening Visit. With the exception of troponin I, testing may be repeated once to see if value returns to within range but any such laboratory abnormality must be resolved by the first day of the screening PSG session (visit 2).Testing can not be repeated if the troponin I value is above the sponsor-specified limit (0.3ng/ml) and the subject should be referred to the treating physician for further evaluation as appropriate. 20. Has any laboratory abnormality that in the investigator's judgment is considered to be clinically significant and not resolved by the first day of the screening PSG session. 21. Is not euthyroid as evidenced by normal TSH. Subjects maintained on thyroid medication must be euthyroid for a period of at least six months prior to the Screening Visit; with no dose changes. 22. Body mass index of 34 or more at the Screening Visit.
23. Apnea-hypopnea index of 10 or more/hour of sleep on Night 1 screening PSG.
24. Periodic limb movements with arousal of 10 or more/hour of sleep on Night 1 screening PSG. 25. Consumption of beverages containing a total 300 mg or more per day on average of caffeine or other xanthines over the preceding 1 month
26. Smoking more than one pack of cigarettes (20) per day on average over the month preceding the Screening Visit, or routinely a smoker after going to bed.
27. Typical consumption of more than 14 alcoholic units in any week, or more than five alcoholic units in any single day, over the month preceding the Screening Visit
28. Use of any psychotropic medications that may affect sleep/wake function within one week or five half-lives (whichever is longer) prior to the Screening Visit or need to use any of these medications at any time during the study. 29. Has received chronic therapy with systemic corticosteroids within 12 months prior to the Screening Visit. 30. Has taken drugs that interact with CYP3A4, CYP2C8 or the P-glycoprotein pathway within two weeks or five half lives, (whichever is longer) prior to the screening PSG session.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Latency to persistent sleep (LPS), as a mean of PSG recordings obtained on two consecutive nights. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
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