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

NCT04114656 | Terminated Phase 1 Results

• 2 other identifiers: 2099732019-002609-23
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Pain

Keywords

GSK3858279; Crossover study; Pain assessment; Placebo-controlled; Intravenous

Outcome Measures

Primary Outcomes (3)

• Posterior Median Ratio to Baseline of Area Under the Curve (AUC 1-8 Days) in Ultraviolet B (UVB) Heat Pain Detection

  Thermal pain tests performed first on normal skin contralateral to site of UVB irradiation then on UVB irradiated skin.A 30\*30 millimeter(mm)thermode was placed on participant's back. Initial temperature of thermode was 32 degree Celsius(C)and increased by 0.5 degree C/second until participant indicated painful stimulus(pain detection threshold indicated by pushing a button on hand-held feedback control or when temperature of 50 degree C reached).AUC ratio to Baseline derived from log change from Baseline in temperature versus(vs)time of study period calculated via trapezoidal method \&normalized \& back transformed(exponential)to get ratio to Baseline. Baseline was mean value of 2 assessments taken before each dosing(Day 1).Posterior Median Ratio to Baseline derived from Bayesian analysis updating prior(non-informative)with information collected from study(likelihood).Data reported as 'Median' refers to 'Posterior Median' and '95% Confidence Interval' refers to '95% Credible Interval'.

  Baseline (Day 1) and up to Day 8

• Posterior Median Ratio to Baseline of AUC (1-15 Days) in Cold Pressor Time to Intolerable Pain Threshold

  Participants put non-dominant hand in water bath at 35+/-0.5 degree C.Blood pressure cuff on upper arm inflated to 20mm of Mercury below resting diastolic pressure. Participants then removed hand \& directly placed in similar-size bath(1.0+/-0.5 degree C).Participants indicated increase in pain intensity by moving electronic Visual Analogue scale(eVAS) slider when pain detection threshold was reached(first change in sensation from cold non-painful to painful).When pain tolerance was reached, participants removed their hand\& blood pressure cuff was deflated.AUC ratio to Baseline derived from log change from Baseline in time to intolerable pain vs time of study period calculated via trapezoidal method \&normalized and back transformed(exponential) to get ratio to Baseline.Baseline was mean value of 2 assessments taken before each dosing(Day 1).Posterior Median Ratio to Baseline derived from Bayesian analysis updating prior(non-informative)with information collected from study(likelihood).

  Baseline (Day 1) and up to Day 15

• Posterior Median Ratio to Baseline of AUC (1-15 Days) in Electrical Pain Tolerance Threshold (Single Stimulus)

  Two electrodes were placed on clean (scrubbed) skin overlying left tibial bone 100mm distal from caudal end of patella to detect cutaneous electrical pain. Each stimulus(10-Hertz \[Hz\] tetanic pulse with duration of 0.2 milliseconds) was controlled by a computer-controlled constant current stimulator.Pain intensity after each stimulation was measured using eVAS,until pain tolerance level was reached,or maximum of 50 milliamper(mA) was reached. AUC ratio to Baseline derived from log change from Baseline in mA versus time of study period calculated via trapezoidal method and normalized and back transformed(exponential)to get ratio to Baseline. Baseline was mean value of 2 assessments taken before dosing(Day 1).Posterior Median Ratio to Baseline derived from Bayesian analysis updating prior (non-informative) with information collected from study(likelihood).Data reported as 'Median' refers to'Posterior Median'and data reported as'95% Confidence Interval' refers to '95% Credible Interval'.

  Baseline (Day 1) and up to Day 15

Study Arms (2)

Participants receiving Placebo

PLACEBO COMPARATOR

All participants will receive a single dose of placebo in either one or two of the three study periods, as per the randomization schedule.

Drug: Placebo

Participants receiving GSK3858279

EXPERIMENTAL

All participants will receive a single dose of GSK3858279 in either one or two of the three study periods, as per the randomization schedule.

Drug: GSK3858279

Interventions

Placebo DRUG

Placebo will be available as intravenous (IV) infusion of normal saline (0.9 percent \[%\] sodium chloride solution).

Participants receiving Placebo

GSK3858279 DRUG

GSK3858279 will be available as IV infusion and the dose level to be administered is 3 milligrams (mg) per kilogram (kg).

Participants receiving GSK3858279

Eligibility Criteria

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

You may qualify if:

• Participants must be 18 to 50 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 kg and body mass index (BMI) within the range 18 to 30 kg per meter square (kg/m\^2) (inclusive).
• Must be male participants: Participants must agree to the following during the intervention period and for at least 90 days after the last dose of study intervention:
• Refrain from donating sperm plus, either
• 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
• Must agree to use contraception/barrier as detailed below:
• (i) Agree to use a male condom. (ii) 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.
• 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.

You may not qualify if:

• 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.
• Personal or family history of cardiomyopathy.
• Abnormal blood pressure as determined by the investigator.
• Symptomatic herpes zoster within 3 months prior to screening.
• 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.
• Significant allergies to humanized monoclonal antibodies.
• 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).
• Lymphoma, leukemia, or any malignancy. Those who are at risk of deoxyribonucleic acid (DNA) repair diseases or any family history of DNA repair disease.
• Alanine transaminase (ALT) greater than (\>)1.5 times upper limit of normal (ULN).
• Bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than \[\<\]35%).
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Corrected QT interval (QTc) \>450 msec.
• History of Stevens-Johnson syndrome.
• Known immunodeficiency.
• Participants with an acute, recurrent or chronic infection (for example, osteomyelitis), who have been receiving treatment within three months prior to dosing or individuals with an active infection.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Leiden, 2333 CL, Netherlands

Location

MeSH Terms

Conditions

Pain

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2019
• First Posted: October 3, 2019
• Study Start: October 15, 2019
• Primary Completion: September 16, 2021
• Study Completion: September 16, 2021
• Last Updated: March 18, 2024
• Results First Posted: August 1, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data 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.

Locations

NL (1)