Phase1 Study of GR121167, Single and Multiple Dose Study in Healthy Japanese Males

Influenza, Human Clinical Trial

Official title:

Phase1 Study of GR121167- A Double Blind, Placebo Controlled, Randomized, Dose Ascending, Single and Multiple Dose Study to Investigate the Safety and Pharmacokinetics Following Intravenous Administration of GR121167 in Healthy Japanese Males-

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01428479
• Other study ID #: 115070
• Status: Completed
• Phase: Phase 1
• First received: June 23, 2011
• Last updated: July 18, 2017
• Start date: January 7, 2011
• Est. completion date: April 4, 2011

Study information

• Verified date: July 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a randomized, double-blind, ascending dose, placebo-controlled, incomplete crossover, single and multiple dose study in healthy Japanese male subjects to assess the pharmacokinetics and safety/tolerability of single and multiple intravenous administration of GR121167. Serial blood samples and pooled urine samples for the determination of GR121167 concentration will be collected and safety assessments will be performed for each treatment period.

The pharmacokinetics and dose proportionality of GR121167 after single intravenous administration of GR121167 at the dose levels of 100 mg, 300 mg and 600 mg will be assessed. In addition, in the final treatment period (600 mg), twice daily intravenous administrations for 5 days will be also conducted and the pharmacokinetics and accumulation will be assessed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: April 4, 2011
• Est. primary completion date: April 4, 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Healthy as defined as being free from clinically significant illness or disease as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, vital sign, laboratory tests and ECG.

2. Japanese healthy male between 20 and 55 years of age inclusive, at the time of signing the informed consent.

3. Body weight >= 50.0 kg and BMI within the range 18.5<= - <25.0 kg/m2 (inclusive).

4. A creatinine clearance >= 80ml/min as determined by Cockcroft-Gault equation:CLcr (mL/min) = (140 - age) * Wt / (72 * Scr). Where age is in years, weight (wt) is in kg, and serum creatinine (Scr) is in units of mg/dl. [Cockcroft, 1976]

5. Non-smoker or ex-smoker having ceased smoking for at least 6 months.

6. AST, ALT, alkaline phosphatase and total bilirubin =< ULN at screening.

7. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

1. A positive test for syphilis, Hepatitis B surface antigen or positive Hepatitis C antibody, HIV antigen /antibody, HTLV-1 at screening

2. A positive pre-study drug screen at screening.

3. History of regular alcohol consumption exceeding, on average, 14 drinks/week for men (1 drink = 5 ounces (150 mL) of wine or 350 mL of beer or 1.5 ounces (45 mL) of 80 proof distilled spirits) within 6 months of screening.

4. The subject had participated in a clinical study or post-marketing study with an investigational or a non-investigational product during the previous 4 months preceding the first dose of study medication of this study

5. The subject planned to concurrently participate in another clinical study or post-marketing study.

6. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study medication.

7. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy excluding pollen allergy without current symptoms.

8. Where participation in the study would result in donation of blood or blood products in excess of 400 mL within 4 month or 200 mL within 2 months.

9. Unwillingness or inability to follow the procedures outlined in the protocol.

10. Consumption of red wine, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.

11. Single QTcB >= 450 msec; at screening

12. Subjects with ECG results considered clinically significant by the investigator.

13. Subjects with a personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes or additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia).

14. Subjects with a family history of sudden cardiac death.

15. Subjects with a supine systolic blood pressure <90mmHg or >140mmHg and/or a supine diastolic blood pressure <55mmHg or >90mmHg and/or systolic blood pressure drop from supine to standing of >30mmHg.

16. History of renal failure or renal dysfunction

Related Conditions & MeSH terms

• Influenza, Human

Intervention

Drug:
• GR121167 Solution
GR121167 solution will be administered intravenously. For 100 mg subject will receive 10 milliliter (mL) of solution, 30 mL for 300 mg and 60 mL for 600 mg
• Placebo
Placebo solution will be administered intravenously.

Locations

Country	Name	City	State
Japan	GSK Investigational Site	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Profile of pharmacokinetics	Cmax, AUC0-inf, AUC0-last, AUC0-12, C12 (Ct), accumulation ratios (Ro, Rs)	Pre, 0.5, 0.75, 1, 1.5, 2, 4, 6 ,8 ,10 ,12 ,24 hrs after single dose and 5 days multiple dose, and at the trough during multiple doses
Primary	Safety parameters	vital signs, ECGs, clinical laboratory tests, and adverse events	upto 24 hrs after dose and 7 days after final dose
Secondary	Profile of urinary pharmacokinetics	Ae, fe, CLr	0-4, 4-8, 8-12, 12-24hrs after single dose
Secondary	Profile of serum pharmacokinetics	AUC0-24, %AUCex, ?z, tmax, t1/2, CL, Vz, Vss	Pre, 0.5, 0.75, 1, 1.5, 2, 4, 6 ,8 ,10 ,12 ,24 hrs after single dose and 5 days multiple dose

External Links

•   Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
•   Results for study 115070 can be found on the GSK Clinical Study Register.