Last updated: 07/09/2021 10:20:09

Study to investigate safety, tolerability, pharmacodynamics and pharmacokinetics of GSK2646264

GSK study ID
200196
See study documents
Clinicaltrials.gov ID
NCT02424799
See results summary
EudraCT ID
2014-001015-39
EU CT Number
Not applicable
Trial status
Completed
Completed
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A randomised double blind (sponsor unblinded), single and repeat ascending dose First Time in Human study in healthy subjects, cold urticaria and chronic spontaneous urticaria subjects to investigate safety, tolerability, pharmacodynamics and pharmacokinetics of GSK2646264
Trial description: This First Time in Human (FTIH) study, which will be performed in three parts, is designed to investigate the safety, local tolerability, pharmacokinetics and pharmacodynamics after single and repeat topical applications of up to 2 strengths of GSK2646264 and corresponding placebo within the same subject, in healthy adult subjects (Part A), subjects with cold urticaria (CU, Part B) and subjects with chronic spontaneous urticaria (CsU, Part C). The study will also measure short term effects of GSK2646264 on the number and size of weals in subjects with CsU, and in healthy subjects and subjects with CU following provocation tests.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Number of participants with adverse events (AEs) and serious AEs (SAEs) Part A

Timeframe: Up to Day 7

Number of participants with AEs and SAEs Part A

Timeframe: Up to Day 11

Number of participants with AEs and SAEs Part B

Timeframe: Up to Day 19

Number of participants with AEs and SAEs Part C

Timeframe: Up to Day 23

Number of participants with AEs and SAEs defined by severity Part A

Timeframe: Up to Day 7

Number of participants with AEs and SAEs defined by severity Part A

Timeframe: Up to Day 11

Number of participants with AEs and SAEs defined by severity Part B

Timeframe: Up to 19 days

Number of participants with AEs and SAEs defined by severity Part C

Timeframe: Up to 23 days

Change from Baseline in vital sign parameter heart rate for Part A

Timeframe: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 and follow-up (Day 5 to Day 7)

Change from Baseline in vital sign parameter heart rate for Part A

Timeframe: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (pre-dose), Day 5, Day 6, Day 7, Day 8 and follow-up (Day 9 to Day 11)

Change from Baseline in vital sign parameter heart rate for Part B

Timeframe: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to Day 19)

Change from Baseline in vital sign parameter heart rate for Part C

Timeframe: Baseline and (Day 1 pre-dose), Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15, follow-up (Day 23)

Change from Baseline in vital sign parameters systolic blood pressure (SBP) and diastolic blood pressure (DBP) for Part A

Timeframe: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 and follow-up (Day 5 to Day 7)

Change from Baseline in vital sign parameters SBP and DBP for Part A

Timeframe: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (pre-dose), Day 5, Day 6, Day 7, Day 8 and follow-up (Day 9 to Day 11)

Change from Baseline in vital sign parameters SBP and DBP for Part B

Timeframe: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to Day 19)

Change from Baseline in vital sign SBP and DBP for Part C

Timeframe: Baseline (Day 1 pre-dose) and Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15 and follow-up (Day 23)

Change from Baseline in electrocardiogram (ECG) parameters for Part A

Timeframe: Baseline (Day -1) and Day 4, and follow-up (Day 5 to Day 7)

Secondary outcomes:
Not applicable
Interventions:
Drug: GSK2646264 0.5% topical cream
Drug: GSK2646264 1% topical cream
Drug: Placebo
Enrollment:
34
Observational study model:
Not applicable
Primary completion date:
2017-10-11
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Urticaria
Product
GSK2646264
Collaborators
Not applicable
Study date(s)
November 2014 to November 2017
Type
Interventional
Phase
1

Participation criteria

Sex
Female & Male
Age
18 - 70 years
Accepts healthy volunteers
No
  • Inclusion criteria for all subjects in Parts A, B and C
  • Male or female subject aged at least 18 years (Yrs) at the time of signing the informed consent. The upper age limit of subjects is defined in the specific inclusion criteria for each cohort.
Inclusion and exclusion criteria
Inclusion criteria:
  • Inclusion criteria for all subjects in Parts A, B and C
  • Male or female subject aged at least 18 years (Yrs) at the time of signing the informed consent. The upper age limit of subjects is defined in the specific inclusion criteria for each cohort.
  • All subjects must be free from scarring or skin markings (e.g. tattoos or piercings) and open wounds (e.g. scarring or skin markings) on the defined areas of the body that cream will be applied onto, unless in the opinion of the investigator it will not compromise the subjects safety and quality of data.
  • Able to refrain from exposure to extended and direct sunlight during the study period, from screening (SCR) until follow up, especially the area that is under treatment during the study.
  • Able to refrain from shaving and waxing the areas on which the study cream will be applied during the duration of the study from SCR to follow up.
  • Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in protocol. This criterion must be followed from the time of the first dose of study medication until the follow up visit or a time period that is 5 terminal half-live post-last dose which will be determined following Part A of the study.
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. Willing, committed and able to return for all clinic visits and complete all study-related procedures. Able to read, understand and complete study- related questionnaires. Inclusion criteria specific for healthy subjects (Part A)
  • The subject is aged between 18 and 55 yrs of age inclusive, at the time of signing the informed consent.
  • Body weight >=50 kilogram (kg) and body mass index (BMI) within the range 19 to 30 kg per square meter (m^2 )(inclusive).
  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator, in consultation with the GSK Medical Monitor (MM) if required, agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Demonstration of a positive weal and flare reaction (>=3 millimeter (mm) in diameter relative to negative control) to at least one allergen from a battery of allergens (mixed grass pollen, Dermatophagoides pteronyssinus, birch pollen and cat dander) on skin prick testing at SCR.
  • Subjects must be free from any past or present benign or malignant skin conditions and disease, unless in the opinion of the investigator it will not compromise the subject’s safety and quality of data.
  • Non–smokers or if the subject is a tobacco smoke: smokes less than 5 cigarettes per day and commits to not smoke tobacco for the duration of the in-house stay, and commits to stable and moderate use (as determined by the Investigator) of tobacco or nicotine-containing products, including nicotine patches/gum, during the course of the study, as long as the patches do not interfere with the study procedures.
  • A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy for this definition, “documented” refers to the outcome of the investigator's/designee’s review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject’s medical records; or postmenopausal defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) >40 milli international unit [MlU]/milliliter [mL] and estradiol <40 picogram (pg)/mL (<147 picomoles/litre) is confirmatory. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods described if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method. Additional Inclusion criteria specific for subjects with CU (Part B)
  • Diagnosed with CU for more than six weeks as confirmed by medical history and with a positive cold stimulation test assessed by TEMPTest 4.0 prior to first dose.
  • The subject is aged between 18 and 70 yrs of age inclusive, at the time of signing the informed consent.
  • Body weight >=50 kg and BMI within the range 19 to 35 kg/m^2 (inclusive).
  • Other than a diagnosis of CU, the subject should have no other co-morbidities which would introduce additional risk factors and will not interfere with the study procedures, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
  • A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator, in consultation with the GSK MM if required, agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedure.
  • In addition, the following criterion will apply to a minimum of 4 patients in Part B: Demonstration of a positive weal and flare reaction (>=3 mm relative to negative control) to at least one allergen from a battery of allergens (mixed grass pollen, Dermatophagoides pteronyssinus, birch pollen and cat dander) on skin prick testing at SCR,
  • Subjects must be free from any past or present benign or malignant skin conditions and disease, other than the specified condition required for eligibility of subjects as defined in the specific inclusion criteria for CU cohort unless in the opinion of the investigator it will not compromise the subjects safety and quality of data.
  • Non–smokers or if the subject is a tobacco smoker: smokes less than 5 cigarettes per day and commits to not smoke tobacco for the duration of the in-house stay, and commits to stable and moderate use (as determined by the Investigator) of tobacco or nicotine-containing products, including nicotine patches/gum, during the course of the study, as long as the patches do not interfere with the study procedures.
  • Female subjects must agree to use one of the contraception methods listed in protocol, 28 days before their SCR visit and until the followup visit or a time period that is 5 terminal half-live post-last dose which will be determined following Part A of the study. Additional Inclusion criteria specific for subjects with CsU (Part C)
  • The subject is aged between 18 and 70 yrs of age inclusive, at the time of signing the informed consent.
  • Body weight >=50 kg and BMI within the range 19 to 35 kg/m2 (inclusive)
  • Subjects who have a score of >14 on the UAS7 questionnaire with between 4-10 weals observed in a defined area of the body will be included in this study. This area must include either both arms, or both legs or both sides of their torso for 7 consecutive days during the SCR period, prior to the Day 1 visit. If a subject has not completed 7 consecutive days of UAS questionnaire prior to dosing on Day 1 due to exceptional circumstances, the SCR period may be extended until the subject has completed 7 consecutive days of UAS questionnaire. This will only be at the discretion of the Investigator.
  • No other aetiology identified for chronic urticaria such as drug-related or inducible urticaria as determined by history, physical examination and laboratory studies.
  • Subjects must be free from any past or present benign or malignant skin conditions and disease, other than the specified condition required for eligibility of subjects as defined in the specific inclusion criteria for CsU cohort unless in the opinion of the investigator it will not compromise the subjects safety and quality of data.
  • Other than a diagnosis of CsU the subject should have no other co-morbidities which would introduce additional risk factors and will not interfere with the study procedures, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
  • A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator, in consultation with the GSK MM if required, agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Female subjects must agree to use one of the contraception methods 28 days before their SCR visit listed in protocol and until the follow-up visit or a time period that is 5 terminal half-live post-last dose which will be determined following Part A of the study. All Cohorts Exclusion Criteria
  • Thyroid stimulating hormone levels outside normal range.
  • Subjects with a history of Graves disease.
  • Subjects with a history of any thyroid cancer.
  • Unable or unwilling to avoid use of topical creams/lotions at sites where medication will be applied. Washing with soap and water will be permitted.
  • Based on averaged corrected QT interval for heart rate (Fridericia's) [QTcF] values of triplicate ECGs obtained over a brief recording period: QTcF > 450 msec; or QTcF >480 milliseconds (msec) in subjects with Bundle Branch Block.
  • Alanine aminotransferase, alkaline phosphatase and bilirubin ≥ 1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) or previous history of uncomplicated cholecystectomy.
  • History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • History of sensitivity to any of the study medications, or components thereof, history of anaphylaxis or a history of drug or other allergy that, in the opinion of the investigator or GSK MM, contraindicates their participation.
  • Unable to refrain from 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 the SCR visit until the completion of the follow-up assessments, unless in the opinion of the Investigator, in consultation with the GSK MM if required, the medication will not interfere with the study procedures or compromise subject safety.
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of SCR.
  • A positive test for HIV antibody.
  • Lactating females.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day
  • Use of topical steroids or calcinurin inhibitors are prohibited during the study from SCR to follow up.
  • Exclusion related to prior drug treatments: Intake of oral corticosteroids within 7 days >10 milligram (mg) per day prior to first SCR visit; Use of depot corticosteroids within 7 days prior to first SCR visit; Subjects who are taking anticoagulants (e.g. warfarin) must not be on warfarin within 21 days prior to SCR. Subjects who are having psoralen combined with ultraviolet A (PUVA) treatment must not be using PUVA treatment within 21 days prior to SCR.
  • Subjects who work for the Sponsor, CRO, or one of the study centres. Country Specific Exclusion criteria for Germany that applies to Part A, Part B and Part C.
  • Subjects who live in detention on court order or on regulatory action, see §40 subsection 1 sentence 3 no. 4 AMG. (Arzneimittelgesetz). Additional Exclusion for Part A – Healthy Subjects
  • Use of H1 antihistamines within 3 days prior to first SCR visit Additional Exclusion for Part B – CU Subjects
  • Exclusion related to prior drug treatments: Use of Zaditen (Ketotifen) within 14 days prior to first SCR visit; Use of Doxepin AZU and other tricyclic antidepressants with antihistaminergic properties within 14 days prior to first SCR visit; Use of H2 antihistamines within 7 days prior to first SCR visit; Use of H1 antihistamines within 7 days prior to first SCR visit; Use of monteleukast or any other leukotriene antagonist within 7 days prior to first SCR visit; Use of biologicals including omalizumab within 5 months prior to first SCR visit. Additional Exclusion for Part C- CsUpatients
  • Exclusion related to prior drug treatments: Intake of cyclosporin within 10 days prior to first SCR visit; Intake of other immunosuppressant drugs within 28 days of first SCR visit; Use of monteleukast or any other leukotriene antagonist within 7 days prior to first SCR visit; Use of Dapsone within 7 days prior to first SCR visit; Use of Zaditen (Ketotifen) within 14 days prior to first SCR visit; Use of Doxepin AZU and other tricyclic antidepressants with antihistaminergic properties within 14 days prior to first SCR visit; Use of H2 antihistamines within 7 days prior first SCR visit; Use of biologicals including omalizumab within 5 months prior to first SCR visit; Use of H1 antihistamines above the licensed dose within 3 days prior to first SCR visit.

Trial location(s)

Location
Status
Contact us
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Location
GSK Investigational Site
Berlin, Germany, 10117
Status
Study Complete
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Location
GSK Investigational Site
Berlin, Berlin, Germany, 14050
Status
Study Complete
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Location
GSK Investigational Site
Norwich, Norfolk, United Kingdom, NR4 7UY
Status
Study Complete
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Location
GSK Investigational Site
London, London, United Kingdom, SE1 9RT
Status
Study Complete
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Location
GSK Investigational Site
London, London, United Kingdom, SE1 9R
Status
Study Complete
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Location
GSK Investigational Site
Norwich, Norfolk, United Kingdom, NR4 7U
Status
Study Complete
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Study documents

Clinical study report
Available language(s): English
Download document(s)
Protocol
Available language(s): English
Download document(s)
Statistical analysis plan
Available language(s): English
Download document(s)

If you wish to request for full study report, please contact - [email protected]

Results overview

Results posted on ClinicalTrials.gov

Recruitment status
Completed
Actual primary completion date
2017-10-11
Actual study completion date
2017-10-11

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

Additional information
Not applicable
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