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Effects of Intravenous GSK3858279 on a Battery of Evoked Pain Tests in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04114656
Recruitment Status : Suspended (Due to the COVID-19 pandemic, this study has temporarily suspended recruitment activities. Other elements of the study are ongoing.)
First Posted : October 3, 2019
Last Update Posted : June 26, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE September 12, 2019
First Posted Date  ICMJE October 3, 2019
Last Update Posted Date June 26, 2020
Actual Study Start Date  ICMJE October 15, 2019
Estimated Primary Completion Date August 13, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 1, 2019)
  • Temperature required to detect Ultraviolet B (UVB) heat pain threshold at Day 1 [ Time Frame: Day 1 ]
    The thermal pain tests will be performed first on normal skin contralateral to the site of UVB irradiation, then on UVB irradiated skin. A thermode will be placed on the participant's back. The initial temperature will be 32 degree Celsius and will be increased by 0.5 degree Celsius per second until the participant indicates the stimulus as painful, or when a temperature of 50 degree Celsius is reached.
  • Temperature required to detect UVB heat pain threshold at Day 2 [ Time Frame: Day 2 ]
    The thermal pain tests will be performed first on normal skin contralateral to the site of UVB irradiation, then on UVB irradiated skin. A thermode will be placed on the participant's back. The initial temperature will be 32 degree Celsius and will be increased by 0.5 degree Celsius per second until the participant indicates the stimulus as painful, or when a temperature of 50 degree Celsius is reached.
  • Temperature required to detect UVB heat pain threshold at Day 8 [ Time Frame: Day 8 ]
    The thermal pain tests will be performed first on normal skin contralateral to the site of UVB irradiation, then on UVB irradiated skin. A thermode will be placed on the participant's back. The initial temperature will be 32 degree Celsius and will be increased by 0.5 degree Celsius per second until the participant indicates the stimulus as painful, or when a temperature of 50 degree Celsius is reached.
  • Time to intolerable pain threshold by cold pressor pain method at Day 1 [ Time Frame: Day 1 ]
    Time to intolerable pain threshold will be assessed by cold pressor pain method. In this method, participants will place their non-dominant hand into a water bath (35 ± 0.5 degree Celsius). After 2 minutes, participant will then move their hand from the warm water bath, directly placing their hand into a similar sized bath (1.0 ± 0.5 degree Celsius). The participants will be instructed to indicate when pain detection threshold is reached; first change in sensation from cold non-painful to painful and the increase in pain intensity. This endpoint will look at the pain tolerance on when it is no longer tolerable (Electronic Visual Analogue Scale [eVAS] slider at 100mm) or when a time limit (120 seconds) is reached.
  • Time to intolerable pain threshold by cold pressor pain method at Day 2 [ Time Frame: Day 2 ]
    Time to intolerable pain threshold will be assessed by cold pressor pain method. In this method, participants will place their non-dominant hand into a water bath (35 ± 0.5 degree Celsius). After 2 minutes, participant will then move their hand from the warm water bath, directly placing their hand into a similar sized bath (1.0 ± 0.5 degree Celsius). The participants will be instructed to indicate when pain detection threshold is reached; first change in sensation from cold non-painful to painful and the increase in pain intensity. This endpoint will look at the pain tolerance on when it is no longer tolerable (Electronic Visual Analogue Scale [eVAS] slider at 100mm) or when a time limit (120 seconds) is reached.
  • Time to intolerable pain threshold by cold pressor pain method at Day 8 [ Time Frame: Day 8 ]
    Time to intolerable pain threshold will be assessed by cold pressor pain method. In this method, participants will place their non-dominant hand into a water bath (35 ± 0.5 degree Celsius). After 2 minutes, participant will then move their hand from the warm water bath, directly placing their hand into a similar sized bath (1.0 ± 0.5 degree Celsius). The participants will be instructed to indicate when pain detection threshold is reached; first change in sensation from cold non-painful to painful and the increase in pain intensity. This endpoint will look at the pain tolerance on when it is no longer tolerable (Electronic Visual Analogue Scale [eVAS] slider at 100mm) or when a time limit (120 seconds) is reached.
  • Time to intolerable pain threshold by cold pressor pain method at Day 15 [ Time Frame: Day 15 ]
    Time to intolerable pain threshold will be assessed by cold pressor pain method. In this method, participants will place their non-dominant hand into a water bath (35 ± 0.5 degree Celsius). After 2 minutes, participant will then move their hand from the warm water bath, directly placing their hand into a similar sized bath (1.0 ± 0.5 degree Celsius). The participants will be instructed to indicate when pain detection threshold is reached; first change in sensation from cold non-painful to painful and the increase in pain intensity. This endpoint will look at the pain tolerance on when it is no longer tolerable (Electronic Visual Analogue Scale [eVAS] slider at 100mm) or when a time limit (120 seconds) is reached.
  • Electrical pain tolerance threshold for single stimulus Day 1 [ Time Frame: Day 1 ]
    For cutaneous electrical pain, two electrodes will be placed on clean (scrubbed) skin overlying the left tibial bone 100 millimeter (mm) distal from the caudal end of the patella. For single (stair) stimulus, each stimulus (10-hertz [Hz] tetanic pulse with a duration of 0.2 millisecond [ms]) will be controlled by a computer-controlled constant current stimulator. The pain intensity after each stimulation will be measured using the eVAS, until pain tolerance level is reached, or a maximum of 50 milliamp (mA) is reached.
  • Electrical pain tolerance threshold for single stimulus at Day 2 [ Time Frame: Day 2 ]
    For cutaneous electrical pain, two electrodes will be placed on clean (scrubbed) skin overlying the left tibial bone 100 millimeter (mm) distal from the caudal end of the patella. For single (stair) stimulus, each stimulus (10-hertz [Hz] tetanic pulse with a duration of 0.2 millisecond [ms]) will be controlled by a computer-controlled constant current stimulator. The pain intensity after each stimulation will be measured using the eVAS, until pain tolerance level is reached, or a maximum of 50 milliamp (mA) is reached.
  • Electrical pain tolerance threshold for single stimulus Day 8 [ Time Frame: Day 8 ]
    For cutaneous electrical pain, two electrodes will be placed on clean (scrubbed) skin overlying the left tibial bone 100 millimeter (mm) distal from the caudal end of the patella. For single (stair) stimulus, each stimulus (10-hertz [Hz] tetanic pulse with a duration of 0.2 millisecond [ms]) will be controlled by a computer-controlled constant current stimulator. The pain intensity after each stimulation will be measured using the eVAS, until pain tolerance level is reached, or a maximum of 50 milliamp (mA) is reached.
  • Electrical pain tolerance threshold for single stimulus at Day 15 [ Time Frame: Day 15 ]
    For cutaneous electrical pain, two electrodes will be placed on clean (scrubbed) skin overlying the left tibial bone 100 millimeter (mm) distal from the caudal end of the patella. For single (stair) stimulus, each stimulus (10-hertz [Hz] tetanic pulse with a duration of 0.2 millisecond [ms]) will be controlled by a computer-controlled constant current stimulator. The pain intensity after each stimulation will be measured using the eVAS, until pain tolerance level is reached, or a maximum of 50 milliamp (mA) is reached.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Intravenous GSK3858279 on a Battery of Evoked Pain Tests in Healthy Volunteers
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled, Three-period Two Treatment Incomplete-block Crossover Study to Investigate the Effects of Intravenous GSK3858279 on a Battery of Evoked Pain Tests in Healthy Participants
Brief Summary This study will evaluate the mechanistic basis for the analgesic effects of GSK3858279 in humans by using a battery of experimental pain assessments in healthy participants. This will be placebo-controlled, three-period two-treatment crossover study. In each period, participants will receive either GSK3858279 or placebo in a 1:1 ratio. Only healthy male participants will be enrolled into the study. The duration of the study will be approximately 6-months.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Pain
Intervention  ICMJE
  • Drug: Placebo
    Participants will be administered 0.9% sodium chloride solution as Placebo. The appropriate volume of placebo will be infused over 1 hour.
  • Biological: GSK3858279
    Participants will be administered GSK3858279 as solution for injection in unit dose strength of 50 milligram (mg) per milliliter (mL). Each vial has an extractable volume of 3 mL (150 mg per vial). The dose level to be administered is 3 mg per kilogram (kg). GSK3858279 may be diluted in normal saline and the appropriate volume will be infused over 1 hour. GSK3858279 is formulated in 0.79 mg per mL sodium acetate, 50 mg per mL Sorbitol, 0.4 mg per mL polysorbate 20, glacial acetic acid 0.28 mg per mL, water for injection, pH 5.0.
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    All participants will receive a single dose of placebo in either one or two of the three study periods, as per the randomization schedule.
    Intervention: Drug: Placebo
  • Experimental: GSK3858279
    All participants will receive a single dose of GSK3858279 in either one or two of the three study periods, as per the randomization schedule.
    Intervention: Biological: GSK3858279
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: October 1, 2019)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 13, 2021
Estimated Primary Completion Date August 13, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participants must be 18 to 45 years of age inclusive, at the time of signing the informed consent.
  • Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and cardiac monitoring.
  • Participants with body weight within 50-100 kilogram (kg) and body mass index (BMI) within the range 18 to 30 kg per meter square (inclusive).
  • Male participants.
  • Participants must agree to refrain from donating sperm. Participants must be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or participants must agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
  • Participants capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

  • Participants with history or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
  • Participants with personal or family history of cardiomyopathy.
  • Participants with abnormal blood pressure as determined by the investigator.
  • Participants with symptomatic herpes zoster within 3 months prior to screening.
  • Participants with evidence of active or latent tuberculosis (TB) as documented by medical history and examination, and TB testing: a positive (not indeterminate) QuantiFERON-TB Gold test.
  • Participants with significant allergies to humanized monoclonal antibodies.
  • Participants with Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A [IgA] dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).
  • Participants with lymphoma, leukemia, or any malignancy. Those who are at risk of deoxyribonucleic acid (DNA) repair diseases or any family history of DNA repair disease.
  • Participants with alanine transaminase (ALT) >1.5 times upper limit of normal (ULN).
  • Participants with bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Participants with current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Participants with electrocardiogram QT interval corrected for heart rate (QTc) >450 millisecond (msec).
  • Participants with history of Stevens - Johnson syndrome.
  • Participants with known immunodeficiency.
  • Participants with a chronic infection (for example, osteomyelitis), who have been receiving treatment within three months prior to dosing or individuals with an active infection.
  • Participants with previous or current history of bleeding diathesis.
  • Participants with previous history of hypertrophic or keloid scarring.
  • Participants with any current, clinically significant, known medical condition in particular any existing conditions that would affect sensitivity to cold (such as atherosclerosis, Raynaud's disease, urticaria, and hypothyroidism) or pain (such as disease that causes pain, hypesthesia, hyperalgesia, allodynia, paraesthesia, neuropathy).
  • Participants indicating pain tests intolerable at screening or achieving tolerance at >80% of maximum input intensity for cold pressor, pressure pain and electrical tests.
  • Participants with history or presence of post-inflammatory hyperpigmentation.
  • Participants with Fitzpatrick skin type IV, V or VI.
  • Participants with any of the following on the proposed test area on the back: widespread acne, freckles, tattoos, birthmarks or scarring (investigator discretion may be used to determine if small areas may be avoided in the testing area on the back).
  • Participants with a minimal erythema dose (MED) higher than 355 millijoule per square centimeter (mJ/cm^2) at screening.
  • Participants with past or intended use of over-the-counter or prescription medication including herbal medications within 7 days prior to screening until after follow-up visit.
  • Participants with live vaccine(s) within 1 month prior to screening or plans to receive such vaccines during the study.
  • Participants with treatment with biologic agents (such as monoclonal antibodies including marketed drugs) or immunosuppressants within 3 months or 5 half-lives (whichever is longer) prior to screening.
  • Participants having treatment with anti-platelet or anti-coagulant agents within 7 days of screening.
  • Participants with major surgery (as per investigator's judgement) within 3 months prior to dosing.
  • Participant has made a blood or plasma donation or has had a comparable blood loss (>450 mL) within the last 3 months prior to the Screening Visit. Blood donation during the study is not permitted.
  • Participants having exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
  • Participants with current enrolment or past participation in any other clinical study involving an investigational study intervention within the last 3 months, 5-half-lives or twice the duration of the biological product before screening in this current study.
  • Participants with presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention.
  • Participants with presence of Hepatitis B core antibody (HbcAb) at screening or within 3 months prior to first dose of study intervention.
  • Participants with positive Hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.
  • Participants with positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention.
  • Participants with abnormal clinically significant echocardiogram at screening, as assessed by the investigator.
  • Participants with cardiac troponin T or N-terminal pro-brain natriuretic peptide (NT-proBNP) levels out of normal range at screening.
  • Participants with positive pre-study drug/alcohol screen.
  • Participants with positive human immunodeficiency virus (HIV) antibody test.
  • Participants with regular use of known drugs of abuse.
  • Participants with estimated glomerular filtration rate (eGFR) of <90 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2) or serum creatinine >1.5 times ULN or urine albumin:creatinine ratio of >300 mg per gram (g) at screening.
  • Participants with regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of >21 units for males. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • Smoker or participants having smoking history or use of tobacco- or nicotine-containing products (for example, nicotine patches or vaporizing devices) within 6 months prior to screening.
  • Participants having sensitivity to heparin or heparin-induced thrombocytopenia.
  • Participants having sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04114656
Other Study ID Numbers  ICMJE 209973
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP