A Repeat Dose Positron Emission Tomography Study With GSK1144814

NCT01209039 | Completed Phase 1

• 1 other identifier: 111587
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

Brief Summary

This study described in the present protocol consists of two parts. Part A is a multiple ascending dose study to evaluate the safety, tolerability and pharmacokinetics of ascending doses of GSK1144814. Part B is an open label design in healthy male subjects to assess the GSK1144814 Neurokinin1 receptor occupancy.

Conditions

Schizophrenia

Keywords

Schizophrenia; PET

Outcome Measures

Primary Outcomes (3)

• PET receptor occupancy

  1 week

• To assess the safety and tolerability by reviewing the number of subjects with adverse events, a review of laboratory samples and a review of vitals.

  2 or 4 weeks

• To review pharmacokinetic data

  2 or 4 weeks

Secondary Outcomes (1)

• To assess potential induction of CYP3A4

  up to 4 weeks

Study Arms (3)

Part A, cohort 1 and 2

EXPERIMENTAL

Part A, Cohorts 1 and 2, will investigate escalating multiple daily doses of GSK1144814 in 19 subjects

Drug: GSK1144814

Part A, cohort 3

EXPERIMENTAL

Cohort 3 will investigate safety, tolerability and PK of a dose of GSK1144814 over a repeat treatment period of 28 days in 18 subjects and a potential drug drug interaction between GSK1144814 and the CYP3A4 sensitive substrate midazolam (in 15 subjects).

Drug: GSK1144814

Part B

EXPERIMENTAL

Part B will assess NK1 receptor occupancy following repeated administration of GSK1144814 given once daily until steady state is obtained

Drug: GSK1144814

Interventions

GSK1144814 DRUG

Multiple daily doses of GSK1144814 for 28 days

Part A, cohort 3

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 clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if, in the opinion of the Investigator, the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Male or female aged between 18 and 65 years (inclusive) for Part A, or male aged between 25 and 55 years (inclusive) for Part B.
• A female subject is eligible to participate in Part A 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 \[FSH\] higher than 40 mIU/mL and oestradiol lower than 40 pg/mL \[lower than 140 pmol/L\] 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 sampling; this interval depends on the type and dosage of HRT. Following confirmation of their post menopausal status, they can resume the use of HRT during the study without the use of a contraceptive method.
• A male subject must agree to use one of the contraception methods listed in Section 8.1.2. This criterion must be followed from the first investigational product dosing day until at least 3 months after receiving the last dose of the investigational product.
• Body weight higher than or equal to 50 kg and body mass index (BMI) within the range 18 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.
• QTcB or QTcF lower than 450 msec.
• Demonstrates no evidence of mental impairment or co morbid psychiatric disorders or suicidal risk (as determined with the Columbia Suicide Severity Rating Scale \[C SSRS\]).

You may not qualify if:

• 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. In addition, subjects with idiopathic haematuria or proteinuria or conditions such as benign orthostatic proteinuria and benign familial haematuria should be excluded from the study).
• History of regular alcohol consumption within 6 months of the study start defined as:
• 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 a half pint (220 mL) of beer or 1 measure (25 mL) of spirits or 1 glass (125 mL) of wine.
• The subject has participated in a clinical trial and has received an investigational product within 3 month prior to the first investigational product dosing day in the current study.
• Exposure to more than four new chemical entities within 12 months prior to the first investigational product 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 receiving the first dose of the investigational product, 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 sensitivity to any of the investigational products, 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 in the study.
• Where participation in the study would result in donation of blood or blood products in excess of 600 mL within a 56 day period.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• History or presence of clinically significant cardiac arrhythmias, or other clinically significant cardiac disease.
• Smokers confirmed by a positive urinary cotinine test (greater than the local laboratory lower limit of quantification \[LLQ\] of 200 ng/mL or lower). Urine cotinine levels will be measured during Screening and at Baseline.
• Consumption of Seville oranges (including marmalade) and/or grapefruit and/or Chinese grapefruit (pomelo) and/or grapefruit hybrids and/or exotic citrus fruits and/or their fruit juices from 7 days prior to the first investigational product dosing day.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Harrow, Middlesex, HA1 3UJ, United Kingdom

Location

GSK Investigational Site

London, W12 ONN, United Kingdom

Location

Related Links

• Results for study 111587 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 30, 2010
• First Posted: September 24, 2010
• Study Start: July 1, 2009
• Primary Completion: October 25, 2009
• Study Completion: October 25, 2009
• Last Updated: June 20, 2017

Record last verified: 2017-06

Locations

GB (2)