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

NCT00605852 | Completed Phase 1

• 1 other identifier: HH3110161
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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

Conditions

Rhinitis, Allergic, Seasonal

Keywords

Allergic rhinitis; first time in human

Outcome Measures

Primary Outcomes (2)

• ECG monitoring during 24 hours after each dose in the single dose cohorts and on days 1 and 7 in the repeat dose cohorts.

  during 24 hours after each dose in the single dose cohorts and on days 1 and 7 in the repeat dose cohorts.

• Heart rate and blood pressure changes over 24 hours after dosing in single and repeat dose cohorts

  over 24 hours after dosing in single and repeat dose cohorts

Secondary Outcomes (4)

• Change in plasma drug concentration (AUC, Cmax, t1/2, tmax)

  over 24 hours after dosing

• Changes in histamine-induced wheal and flare measurements

  over 24 hours after dosing

• Derived pharmacokinetic parameters for GSK835726 including area under the plasma drug concentration versus time curve (AUC(0-t), AUC(0-¥)), maximum observed plasma drug concentration (Cmax),

  over 24 hours after dosing

• time to maximum observed plasma drug concentration (tmax), apparent clearance (CL/F) and terminal half life (t1/2) following single and repeat oral dosing.

  over 24 hours after dosing

Study Arms (4)

Subjects receiving treatment in cohort I

EXPERIMENTAL

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

Drug: GSK835726; Drug: Placebo

Subjects receiving GSK835726 in cohort II

EXPERIMENTAL

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

Drug: GSK835726

Subjects receiving placebo in cohort II

PLACEBO COMPARATOR

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

Drug: Placebo

Subjects receiving treatment in cohort III

EXPERIMENTAL

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

Drug: GSK835726; Drug: Placebo

Interventions

GSK835726 DRUG

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

Subjects receiving GSK835726 in cohort II; Subjects receiving treatment in cohort I; Subjects receiving treatment in cohort III

Placebo DRUG

Placebo will be given to subjects.

Subjects receiving placebo in cohort II; Subjects receiving treatment in cohort I; Subjects receiving treatment in cohort III

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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."

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

London, NW10 7EW, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 22212854 BACKGROUND

Related 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 HH3110161 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Rhinitis, Allergic, Seasonal; Rhinitis, Allergic

Interventions

GSK 835726

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2008
• First Posted: January 31, 2008
• Study Start: October 29, 2007
• Primary Completion: May 3, 2008
• Study Completion: May 3, 2008
• Last Updated: August 21, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)