Phase 1
N=17
Study to Investigate Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of GSK2646264
Urticaria
Bottom Line
View on ClinicalTrials.gov: NCT02424799 ↗Enrolled (actual)
17
Serious AEs
0.0%
Results posted
Jun 2019
Primary outcome: Primary: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Part A — 4; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- GSK2646264 0.5% topical cream (Drug); GSK2646264 1% topical cream (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Nov 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Part A |
4; 0 | — |
| PRIMARY Number of Participants With AEs and SAEs Part A |
4; 0 | — |
| PRIMARY Number of Participants With AEs and SAEs Part B |
1; 3; 0; 3; 0; 0 | — |
| PRIMARY Number of Participants With AEs and SAEs Part C |
1; 1; 0; 0 | — |
| PRIMARY Number of Participants With AEs and SAEs Defined by Severity Part A |
3; 1; 0 | — |
| PRIMARY Number of Participants With AEs and SAEs Defined by Severity Part A |
3; 1; 0 | — |
| PRIMARY Number of Participants With AEs and SAEs Defined by Severity Part B |
1; 2; 0; 2; 0; 1 | — |
| PRIMARY Number of Participants With AEs and SAEs Defined by Severity Part C |
1; 1; 0; 0; 0; 0 | — |
| PRIMARY Change From Baseline in Vital Sign Parameter Heart Rate for Part A |
-2.1; 1.0; -0.8; -1.9; 1.0; 2.0 | — |
| PRIMARY Change From Baseline in Vital Sign Parameter Heart Rate for Part A |
-2.1; 1.0; -0.8; -1.9; 1.0; 2.0 | — |
| PRIMARY Change From Baseline in Vital Sign Parameter Heart Rate for Part B |
8.0; -1.1; 10.0; -0.9; 4.0; 2.9 | — |
| PRIMARY Change From Baseline in Vital Sign Parameter Heart Rate for Part C |
16.0; 4.8; 4.0; 2.3; 20.0; 8.5 | — |
| PRIMARY Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A |
-0.1; -0.9; -1.1; 4.1; -0.3; 0.6 | — |
| PRIMARY Change From Baseline in Vital Sign Parameters SBP and DBP for Part A |
1.0; 1.8; 1.8; -2.9; -3.9; 0.3 | — |
| PRIMARY Change From Baseline in Vital Sign Parameters SBP and DBP for Part B |
8.3; 2.0; -1.7; 0.6; 3.3; -1.3 | — |
| PRIMARY Change From Baseline in Vital Sign SBP and DBP for Part C |
-10.0; -5.5; -10.0; -4.5; -10.0; 5.3 | — |
| PRIMARY Change From Baseline in Electrocardiogram (ECG) Parameters for Part A |
7.75; 4.00; 0.25; 3.25; -5.13; -1.75 | — |
| PRIMARY Change From Baseline in Electrocardiogram (ECG) Parameters for Part A |
7.75; 4.00; 0.25; 3.25; -5.13; -1.75 | — |
| PRIMARY Change From Baseline in ECG Parameters for Part B |
-6.67; 5.56; 3.33; -2.22; -6.00; -2.44 | — |
| PRIMARY Change From Baseline in ECG Parameters for Part C |
10.00; 1.50; -10.00; -3.50; -14.00; -1.00 | — |
| PRIMARY Number of Participants With Clinical Chemistry Data Outside the Range of Potential Clinical Importance (PCI) for Part A |
1 | — |
| PRIMARY Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part A |
1; 1; 1; 1 | — |
| PRIMARY Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B |
1; 1; 3; 1; 0; 1 | — |
| PRIMARY Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C |
1; 0; 0; 1; 0; 1 | — |
| PRIMARY Number of Participants With Hematology Data Outside the Range of PCI for Part A |
7; 8; 8; 0; 1; 1 | — |
| PRIMARY Number of Participants With Hematology Data Outside the Range of PCI for Part A |
7; 8; 8; 0; 1; 1 | — |
| PRIMARY Number of Participants With Hematology Data Outside the Range of PCI for Part B |
3; 9; 3; 9; 0; 1 | — |
| PRIMARY Number of Participants With Hematology Data Outside the Range of PCI for Part C |
1; 3; 1; 3; 1; 2 | — |
| PRIMARY Number of Participants With Tolerability Assessment for Part A |
9; 8; 6; 8; 0; 1 | — |
| PRIMARY Number of Participants With Tolerability Assessment for Part B |
0; 0; 2; 6; 0; 1 | — |
| PRIMARY Number of Participants With Tolerability Assessment for Part C |
1; 4; 0; 0; 0; 0 | — |
| SECONDARY Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A |
0.00000; 0.00000; 0.02780; 0.19470; 0.31849; 0.49735 | — |
| SECONDARY Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A |
0.00000; 0.00000; 0.02780; 0.19470; 0.31849; 0.49735 | — |
| SECONDARY Plasma GSK2646264 PK Concentrations for Part B |
0.00000; 0.00000; 0.00000; 0.01083; 0.61280; 0.21290 | — |
| SECONDARY Plasma GSK2646264 PK Concentrations for Part C |
0.00000; 0.18048; 1.22397; 1.37440; 2.33635; 2.77940 | — |
| SECONDARY Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of GSK2646264 for Part A |
0.5411; 3.1462; 15.2614 | — |
| SECONDARY AUC (0-t) of GSK2646264 for Part A |
8.6870; 31.0600; 60.2293; 382.4520 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of GSK2646264 for Part A |
0.07360; 0.25084; 0.90382 | — |
| SECONDARY Cmax of GSK2646264 for Part A |
0.72391; 1.96715; 3.28320; 5.22144 | — |
| SECONDARY Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of GSK2646264 for Part A |
97.8835 | — |
| SECONDARY Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of GSK2646264 for Part A |
97.8835 | — |
| SECONDARY Time to Cmax (Tmax) of GSK2646264 for Part A |
19.60; 21.52; 20.32 | — |
| SECONDARY Tmax of GSK2646264 for Part A |
23.85; 23.83; 22.29; 28.99 | — |
| SECONDARY Terminal Half-life (t1/2) of GSK2646264 for Part A |
NA | — |
| SECONDARY t1/2 of GSK2646264 for Part A |
NA | — |
| SECONDARY AUC [0-t] of GSK2646264 for Part B |
40.5235; 18.7840; 100.6152; 46.5654; 825.1809; 379.8602 | — |
| SECONDARY Cmax of GSK2646264 for Part B |
2.71563; 1.30673; 5.14144; 2.41207; 7.51684; 2.89771 | — |
| SECONDARY AUC (0-24) of GSK2646264 for Part B |
34.4377; 166.6914; 68.2224 | — |
| SECONDARY Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of GSK2646264 for Part B |
844.3091; 390.7973 | — |
| SECONDARY Terminal Half-life (t1/2) of GSK2646264 for Part B |
59.69; 64.01 | — |
| SECONDARY Tmax of GSK2646264 for Part B |
19.67; 17.85; 16.93; 21.13; 13.33; 12.62 | — |
| SECONDARY Cmax of GSK2646264 for Part C |
1.85336 | — |
| SECONDARY Tmax of GSK2646264 for Part C |
4.10 | — |
| SECONDARY t1/2 of GSK2646264 for Part C |
NA | — |
Summary
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.
Eligibility 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]/mill
Data sourced from ClinicalTrials.gov (NCT02424799). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.