Pharmacokinetics, Effect of Food, Safety and Tolerability of a New Tablet Formulation of GSK1144814 in Healthy Subjects

NCT01090440 | Completed Phase 1

• 1 other identifier: 112891
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

GSK1144814 is a potent, insurmountable antagonist at human neurokinin-1 (NK1) and neurokinin-3 (NK3) receptors with the potential to treat multiple symptom domains of schizophrenia and be an efficacious antidepressant. This study will be an open label, randomised, three-way cross-over study to evaluate the safety, tolerability and pharmacokinetics of a new tablet formulation of GSK1144814 and to evaluate the effect of food on single oral doses of GSK1144814 in healthy male and female subjects.

Conditions

Schizophrenia

Keywords

schizophrenia; GSK1144814; effect of food; healthy subjects; depressive disorder; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics: tlag, Cmax, tmax, AUC(0-24), AUC(0 t), t½ and AUC(0 to infinity).

  2 months

Secondary Outcomes (1)

• Safety and tolerability: AE monitoring, vital signs (blood pressure, heart rate, body temperature, electrocardiograms (ECGs) (12 lead and Holter), clinical laboratory assessments (standard laboratory parameters).

  2 months

Study Arms (1)

Three-way cross- over

EXPERIMENTAL

Three regimens will be administered in this study: A: GSK1144814 Tablet (100mg) Fasted State; B: GSK1144814 Tablet (200mg) Fasted State and C: GSK 1144814 Tablet (100mg) Fed State (FDA high fat breakfast).

Drug: GSK1144814

Interventions

GSK1144814 DRUG

This study is an open label, randomised, three-way cross-over study to evaluate the pharmacokinetics, effect of food, safety and tolerability of a new tablet formulation of GSK1144814 in healthy male and female (non-child bearing potential) subjects. Sixteen subjects will be enrolled to provide a minimum number of 12 evaluable subjects. The doses to be administered will be 100 mg and 200mg in the fasted state, and 100mg following a high fat breakfast.

Three-way cross- over

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinically significant abnormality or laboratory parameters significantly outside the reference range for the population being studied may be included only if the Investigator and the and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Male or female between 18 and 65 years of age.
• A female subject is eligible to participate if she is of:
• Non childbearing potential defined as pre menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \[FSH\] greater than 40 mIU/mL and oestradiol less than 40 pg/mL \[less than 140 pmol/L\] is confirmatory).
• Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to discontinue HRT to allow confirmation of post menopausal status prior to study enrolment. For most forms of HRT, at least 2 to 4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
• Male subjects must agree to use one of the contraception methods alloed by the protocol. This criterion must be followed from the first dosing day until 3 months after the last dose.
• Body weight greater than or equal to 50 kg and BMI within the range 19 to 29.9 kg/m2 (inclusive).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Demonstrates no evidence of mental impairment or co-morbid psychiatric disorders

You may not qualify if:

• History or presence of clinically significant cardiac arrhythmias, or other clinically significant cardiac disease.
• QTcB or QTcF greater than 450 msec.
• Subjects, who in the investigator's judgement, pose a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behavior and/or any suicidal ideation of type 4 or 5 on the C-SSRS in the last 6 months.
• The subject has a positive pre study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
• A positive pre study hepatitis B surface antigen (HBsAg) or positive hepatitis C virus (HCV) antibody test result within 3 months of Screening.
• A positive test result for antibodies to human immunodeficiency virus (HIV) 1/2.
• Significant renal abnormality (from medical history or as indicated by laboratory investigations). Additionally subjects with idiopathic haematuria or proteinuria or conditions such as benign orthostatic proteinuria and benign familial haematuria should be excluded from the study.
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco or nicotine containing products within 6 months prior to Screening.
• Subjects, who in the investigator's judgement, pose a significant homicidal risk or have ever been homicidal.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• Use of prescription or non prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) 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.
• History of regular alcohol consumption within 6 months of the study defined as the following Australian guidelines:
• An average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to 270ml of full strength beer, 470ml of light beer, 30ml of spirits and 100ml of wine.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

Related Links

• Results for study 112891 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Schizophrenia; Depressive Disorder

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Mood Disorders

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2010
• First Posted: March 22, 2010
• Study Start: September 1, 2009
• Primary Completion: October 9, 2009
• Study Completion: October 9, 2009
• Last Updated: June 22, 2017

Record last verified: 2017-06

Locations

AU (1)