Investigation Of a New Oral Anti-Histamine in Healthy Male Subjects

NCT ID: NCT00605852

Last Updated: 2017-08-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-29
• Study Completion Date: 2008-05-03

Brief Summary

This study is designed to assess the safety and tolerability of single, escalating oral doses and repeat oral doses (7 days, once daily) of GSK835726 in healthy male subjects

Detailed Description

A double-blind, placebo controlled, randomized cross-over single dose escalation study and a double-blind, placebo controlled, randomised parallel group 7-days once daily repeat dose study to investigate safety, tolerability, pharmacokinetics and pharmacodynamics of oral H1/H3 dual antagonist compound in healthy male subjects

Conditions

Rhinitis, Allergic, Seasonal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT

Study Groups

Subjects receiving treatment in cohort I

Eligible subjects will receive three single doses of GSK835726 and one single dose of placebo in cohort I.

Group Type: EXPERIMENTAL

GSK835726

Intervention Type: DRUG

GSK835726 will be available in single dose and repeat dose formulations.

Placebo

Intervention Type: DRUG

Placebo will be given to subjects.

Subjects receiving GSK835726 in cohort II

Eligible subjects will receive repeat doses of GSK835726 once daily for 7 days.

Group Type: EXPERIMENTAL

GSK835726

Intervention Type: DRUG

GSK835726 will be available in single dose and repeat dose formulations.

Subjects receiving placebo in cohort II

Eligible subjects will receive repeat doses of placebo once daily for 7 days.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be given to subjects.

Subjects receiving treatment in cohort III

Eligible subjects will receive two single doses of GSK835726 and one single dose of placebo in cohort III.

Group Type: EXPERIMENTAL

GSK835726

Intervention Type: DRUG

GSK835726 will be available in single dose and repeat dose formulations.

Placebo

Intervention Type: DRUG

Placebo will be given to subjects.

Interventions

GSK835726

GSK835726 will be available in single dose and repeat dose formulations.

Intervention Type: DRUG

Placebo

Placebo will be given to subjects.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male aged between 18 and 50 years inclusive.
• Body mass index within the range 19-29kg/m2 (inclusive), with weight range of 55kg-100kg (inclusive).
• Healthy (defined as individuals who are free from significant nasal, cardiac, pulmonary, gastrointestinal, hepatic, renal, haematological, malignancy, endocrine, neurological and psychiatric disease as determined by history, physical examination and screening investigations).
• Non-smoking status as verified by urinary cotinine levels below 300 ng/mL cotinine at the screening visit. This can include ex-smokers who have given up smoking for >1 year.
• Subjects to be entered in cohorts I and III only: Skin prick test reactivity to histamine of 3mm wheal > than saline control and some associated surrounding erythema.
• Subjects to be entered in cohorts I and III only: Negative skin prick test reactivity to saline control.
• The subject is able and willing to give written informed consent to take part in the study and is available to complete all study measurements.
• If sexually active, male subjects must agree to use a condom with spermicide during sexual intercourse, from the first dose of the study drug until 84 days after the last dose. In addition, female partners of male subjects, who are of childbearing potential, must use a reliable contraceptive method or they must refrain from sexual intercourse from the first dose of study medication until 84 days after the last dose. Reliable forms of contraception include an IUD, condom or diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants, contraceptive patches or a tubal ligation."

Exclusion Criteria

• As a result of the medical interview, physical examination or screening investigations, the Investigator or appropriately qualified designee considers the subject unfit for the study.
• The subject has a history of drug or any other allergy, which, in the opinion of the Investigator or appropriately qualified designee, contraindicates their participation, including known or suspected personal history or family history of adverse reactions or hypersensitivity to anti histamines.
• The subject has participated in a study with a new molecular entity during the previous 3 months or any other study during the previous 2 months.
• The subject regularly, or on average, drinks more than 21 units of alcohol a week or more than an average intake of 3 units per day (One unit = 125ml wine or 25ml spirits or 250ml normal strength lager).
• The subject is currently taking regular (or a course of) medication, prescribed (including all anti-allergy medication) or not (including over the counter medication or herbal remedies such as St Johns Wort). Paracetamol is an exception and will be permitted at daily doses of up to 4g following all doses of investigational product.
• The subject has tested positive for hepatitis C antibody or hepatitis B surface antigen.
• The subject has tested positive for HIV.
• The subject has a positive drugs of abuse and alcohol test.
• Donation of blood (450 mL or more) within 2 months of screening.
• Donation during the study would result in >500mL of blood being donated over a 56 day period
• Significant cardiac conduction abnormalities on two or more ECG tracings separated by at least 5 minutes at screening, including:

• QTc interval > 450 msec
• PR interval > 240 msec
• Evidence of second- or third- degree atrioventricular (AV) block
• Ventricular rate < 45 beats per minute (bpm) or > 100 bpm
• Pathological Q-waves (defined as Q-wave > 40 msec or depth greater than 0.4-0.5 mV)
• Evidence of ventricular pre-excitation
• Evidence of left axis deviation, non-specific intraventricular conduction delay (QRS duration > 120 msec), or complete left bundle branch block
• Subjects with Perennial Allergic Rhinitis (PAR) and Seasonal Allergic Rhinitis (SAR), unless subjects with SAR are asymptomatic and it is outside of the pollen season
• Subjects with dermatographism and other skin conditions that might interfere with the wheal and flare test.
• Subjects who are unable to comply with study procedures.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

London, , United Kingdom

Countries

United Kingdom

References

Daley-Yates P, Ambery C, Sweeney L, Watson J, Oliver A, McQuade B. The efficacy and tolerability of two novel H(1)/H(3) receptor antagonists in seasonal allergic rhinitis. Int Arch Allergy Immunol. 2012;158(1):84-98. doi: 10.1159/000329738. Epub 2011 Dec 29.

Reference Type: BACKGROUND

PMID: 22212854 (View on PubMed)

Study Documents

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

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Other Identifiers

HH3110161

Identifier Type: -

Identifier Source: org_study_id