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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01702467




Registration number
NCT01702467
Ethics application status
Date submitted
4/10/2012
Date registered
8/10/2012
Date last updated
18/10/2017

Titles & IDs
Public title
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single, Oral Escalating Doses of GSK2647544 in Healthy Volunteers
Scientific title
A Single-Blind, Randomized, Placebo-Controlled Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single, Oral Escalating Doses of GSK2647544 in Healthy Volunteers
Secondary ID [1] 0 0
116698
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK2647544
Treatment: Drugs - Placebo

Experimental: GSK2647544 - The starting dose of GSK2647544 is 0.5 mg. The escalating doses to be administered will be determined based on study results from previous dose (s).

Placebo Comparator: Placebo - Matching placebo


Treatment: Drugs: GSK2647544
Capsules containing 0.5mg to 50mg of GSK2647544.

Treatment: Drugs: Placebo
Matching placebo capsules.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability of GSK2647544 as assessed by number of subjects with adverse events (AE)s
Timepoint [1] 0 0
5 days in each of the 4 dosing session
Primary outcome [2] 0 0
Safety and tolerability of GSK2647544 as assessed by change from Baseline in laboratory values
Timepoint [2] 0 0
5 days in each of the 4 dosing session
Primary outcome [3] 0 0
Safety and tolerability of GSK2647544 as assessed by change from Baseline in ECG readings
Timepoint [3] 0 0
5 days in each of the 4 dosing session
Primary outcome [4] 0 0
Safety and tolerability of GSK2647544 as assessed by change from Baseline in Telemetry ECG parameters
Timepoint [4] 0 0
3 Days in each of the 4 dosing session
Primary outcome [5] 0 0
Safety and tolerability of GSK2647544 as assessed by change from Baseline in vital signs
Timepoint [5] 0 0
5 days in each of the 4 dosing session
Primary outcome [6] 0 0
Safety and tolerability of GSK2647544 as assessed by using the Columbia Suicide Severity Rating Scale (C-SSRS)
Timepoint [6] 0 0
5 days in each of the 4 dosing session
Secondary outcome [1] 0 0
Peak plasma concentration (Cmax) of GSK2647544
Timepoint [1] 0 0
4 Days in each of the 4 dosing session
Secondary outcome [2] 0 0
Time of peak plasma concentration (tmax) of GSK2647544
Timepoint [2] 0 0
4 Days in each of the 4 dosing session
Secondary outcome [3] 0 0
Area under the time concentration curve (AUC) of GSK2647544
Timepoint [3] 0 0
4 Days in each of the 4 dosing session
Secondary outcome [4] 0 0
Terminal half-life (t½ ) of GSK2647544
Timepoint [4] 0 0
4 Days in each of the 4 dosing session
Secondary outcome [5] 0 0
Apparent oral clearance (CL/F) of GSK2647544
Timepoint [5] 0 0
4 Days in each of the 4 dosing session
Secondary outcome [6] 0 0
Predose plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and postdose Lp-PLA2 activity
Timepoint [6] 0 0
5 Days in each of the 4 dosing session

Eligibility
Key inclusion criteria
- Healthy males who are 18 to 55 years of age, inclusive

- Healthy as determined by a responsible and experienced physician

- aspartate aminotransferase (AST), Alanine transaminase (ALT), alkaline phosphatase and
bilirubin <= 1.5xUpper Limit of Normal (ULN)

- Average of triplicate QTcB values and average of triplicate QTcF values must both <
450 millisecond (msec)

- Body weight > 50 kg (110 pounds) and body mass index (BMI) between 19 and 30

- Male subjects with female partners of child-bearing potential must agree to use one of
the contraception methods

- Capable of giving written informed consent
Minimum age
18 Years
Maximum age
55 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Those with Lp-PLA2 activity <=20 nanomole/minute/milliliter (mL)(for subjects with 2
known birth parents of at least 50% Japanese, Chinese, or Korean ancestry)

- History of asthma, anaphylaxis or anaphalactoid reactions, severe allergic responses

- History of hypercoagulable state or history of thrombosis

- A history of biliary tract disease including a history of liver disease with elevated
liver function tests of known or unknown etiology

- Positive Human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C at screening

- History of regular use of tobacco- or nicotine-containing products within three months
of the study and/or has a positive breath CO at screening

- History of alcohol consumption exceeding, on average, 21 drinks/week for men (1 drink
= 100 mL of wine or 240 mL of beer or 30 mL of hard liquor in Australia) within 6
months of the first dose of study medication

- Positive urine drug or positive breath alcohol test at screening or at admission to
Clinical Research Unit

- Unable to refrain from use of prescription or non-prescription drugs and vitamins
within 7 days or 5 half-lives (whichever is longer) prior to administration of study

- Unable to refrain from use of dietary/herbal supplements including (but not limited
to) St. John's wort, kava, ephedra (ma huang), gingko biloba, DHEA, yohimbe, saw
palmetto, ginseng and red yeast rice within 14 days prior to treatment with study
medication

- Treatment with an investigational drug within 30 days or 5 half-lives (whichever is
longer) prior to dosing

- Unable to refrain from consumption of grapefruit or grapefruit juice within 7 days
prior to the first dose of study medication

- For male subjects, an unwillingness to abstain from sexual intercourse with pregnant
or lactating women or an unwillingness to use a condom plus partner use of a highly
effective contraceptive if engaging in sexual intercourse with a woman who could
become pregnant until discharge from the study

- Donation of blood in excess of 500 mL within 56 days prior to dosing

- History of sensitivity to heparin or heparin-induced thrombocytopenia

- Subjects, who in the investigator's judgement, pose a significant suicide risk.
Evidence of serious suicide risk may include any history of suicidal behaviour and/or
any suicidal ideation of type 4 or 5 on the C-SSRS in the last 6 months

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/10/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/05/2013
Sample size
Target
Accrual to date
Final
27
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The current study will examine the safety, tolerability, plasma pharmacokinetics (PK), and
plasma pharmacodynamics (PD) of single-doses of GSK2647544.The study will be conducted as a
randomized, single-blind, placebo controlled, 4-way crossover single oral ascending dose
design in 2 independent cohorts, eight healthy male subjects in each of the cohorts. Each
potential subject will undergo Screening visit, Treatment Phase and Follow-up visit.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01702467
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01702467