Last updated: 05/26/2020 11:30:21
An investigation of the safety, tolerability, pharmacokinetics and pharmacodynamics of GSK2245035 in healthy volunteers and allergic rhinitics.
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A randomized, double-blind, placebo-controlled first time into human study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of intranasal dosing with GSK2245035, a TLR7 agonist, in healthy volunteers and allergic rhinitics
Trial description: GSK2245035 is a highly selective Toll-like Receptor 7(TLR7) agonist capable of preferentially inducing the production of interferon alpha (IFNα) versus tumor necrosis factor alpha (TNFα). The aim of this FTIH study is to collect tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) information to enable the identification of appropriate safe doses of intranasal (i.n) GSK2245035, associated with up-regulation of TLR7-mediated genes in the nasal milieu, for use in subsequent clinical drug development studies. There will be two parts to the study: Healthy Volunteers will be dosed in escalating single doses in Part 1, followed by Allergic Rhinitis (AR) subjects dosed similarly in Part 2.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Safety
Timeframe: From screening until follow-up
Nasal Tolerability
Timeframe: From screening until follow-up
TLR7-associated Biomarkers
Timeframe: From pre-dose until 3 days post-dose
Secondary outcomes:
Systemic PK
Timeframe: From pre-dose until 3 days post-dose
Correlation Evaluation
Timeframe: From pre-dose until 3 days post-dose
Interventions:
Drug: 2 ng GSK2445053
Drug: 20ng GSK2445053
Drug: 100ng GSK2445053
Drug: 200ng GSK2445053
Drug: 400ng GSK2445053
Drug: 1000ng GSK2445053
Drug: 2000ng GSK2445053
Drug: 4000ng GSK2445053
Drug: Placebo
Enrollment:
61
Observational study model:
Not applicable
Primary completion date:
2011-30-09
Time perspective:
Not applicable
Clinical publications:
Tsitoura D, Ambery C, Price M, Powley W, Garthside S, Biggadike K, Quint D. Early clinical evaluation of the intranasal TLR7 agonist GSK2245035: use of translational biomarkers to guide dosing and confirm target engagement. Clinical Pharmacology & Therapeutics. 2015;98:369–380.
Medical condition
Rhinitis, Allergic, Seasonal
Product
GSK2245035
Collaborators
Not applicable
Study date(s)
May 2011 to September 2011
Type
Interventional
Phase
1
Participation criteria
Sex
Male
Age
18 - 55 years
Accepts healthy volunteers
Yes
- Inclusion Criteria for all subjects (parts 1 and 2)
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history,physical examination, laboratory testsand cardiac monitoring. A subject with a clinical abnormality or laboratoryparameters outside the reference range for the population being studied may be included only if the Investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Inclusion and exclusion criteria
Inclusion criteria:
- Inclusion Criteria for all subjects (parts 1 and 2)
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history,physical examination, laboratory testsand cardiac monitoring. A subject with a clinical abnormality or laboratoryparameters outside the reference range for the population being studied may be included only if the Investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Male between 18 and 55 years of age inclusive, at the time of signing the informed consent.
- Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 8.1 of the protocol. This criterion must be followed from the time of the first dose of study medication until one week post-dosing.
- Body weight greater than or equal to 50 kilograms (kg) and Body Mass Index (BMI) within the range 19 – 29.9 kilograms per square metre (kg/m2) inclusive.
- 12 lead Electrocardiogram without any clinically significant abnormality as judged by the Investigator, and average QT interval (QTc), QT interval corrected for Basett (QTcB) or QT interval corrected for Fredericia (QTcF) less than 450 milliseconds
- Aspartate transaminase (AST), alanine transamine (ALT), alkaline phosphatase and bilirubin less than 1.5 x Upper Limit of Normal (ULN) (isolated bilirubin greater than1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).
- Subjects have a screening pre-challenge Forced Expiratory Volume in 1 second (FEV1) greater than or equal to 80% and a baseline FEV1/FVC greater than or equal to 70% of the predicted value.
- Subjects should refrain from smoking between screening and the end of the study, and have a negative test for cotinine/ carbon monoxide (CO) at pre-dose.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Available to complete all the required study measurements. Inclusion Criteria for Allergic Rhinitics only (Part 2)
- History and diagnosis of symptomatic seasonal allergic rhinitis to pollen, for more than 3 years.
- Positive skin allergy test (wheal greater than or equal to 4miliimetres) or radioallergosorbent test (RAST) greater than or equal to Class 2, for pollen allergens.
- Subjects have a Total Nasal Symptom Score (TNSS) score of greater than or equal to 3 during the current pollen season (Total nasal symptom score is the sum of nasal congestion, rhinorrhoea, nasal itch and sneeze, each of which are scored on a scale from 0 to 3). Exclusion Criteria for all subjects (Parts 1 and 2):
- History of immunologic or haematologic deficiencies or diseases, except conditions that in the opinion of the Investigator and the GSK Medical Monitor are unlikely to introduce additional risk factors.
- Current diagnosis of asthma.
- Nasal conditions likely to affect the outcome of the study, i.e. nasal septal perforation, nasal polyps, other nasal malformations or history of frequent nosebleeds.
- History of haematologic, gastro-intestinal, hepatic, renal or other condition that may influence the absorption, distribution, metabolism, excretion or action of the drug.
- History of frequent headaches and/or migraine.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- A positive test for Human Immunodeficiency Virus antibody
- A positive screening or pre-dose drug/alcohol screen, or a positive pre-dose smoking test
- History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 21 units for males or greater than 14 units for females. One unit is equivalent to 8 grams (8g) of alcohol: a half-pint or approximately 240 millilitres (240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- The subject has participated in a clinical trial and has received an investigational product within 3 months prior to the first dosing day in the current study.
- Exposure to more than four new chemical entities within 6 months prior to the first dosing day.
- History of drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates participation in this study.
- Donation of blood or blood products in excess of 500 mL within a 90-day period.
- History of sensitivity to heparin or heparin-induced thrombocytopenia
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated Exclusion Criteria for healthy volunteers only (part 1)
- History of rhinitis, including allergic, non-allergic rhinitis and rhinosinusitis. Subjects with recent upper respiratory tract infections (URTIs) will be allowed in the study only if their nasal symptoms have been completely resolved for more than 3 weeks prior to screening.
- 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 entry to the clinic, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. Exclusion criteria for Allergic Rhinitics only (part 2)
- Subjects with recent upper respiratory tract infections (URTIs) will be allowed in the study only if their nasal symptoms have been completely resolved for more than 3 weeks prior to screening.
- Nasal antihistamines: 48 hours
- Oral antihistamines A (cetirizine, fexofenadine, loratadine, desloratadine): 72 hours
- Oral antihistamines B (all others): 72 hours
- Nasal decongestants: 24 hours
- Oral decongestants: 24 hours
- Nasal glucocorticosteroids: 4 weeks
- Oral glucocorticosteroids: 12 weeks
- Oral leukotriene receptor antagonists: 7 days
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 entry into the clinic, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. Subjects using treatment for allergies and AR may participate in the study if they remain free of medication for the following periods of time prior to entry into the clinic:
Trial location(s)
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Completed
Actual primary completion date
2011-30-09
Actual study completion date
2011-30-09
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 114450 can be found on the GSK Clinical Study Register.
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