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Effects of p38 MAPK Inhibitor POLB 001 on in Vivo LPS Challenge Responses

Phase 1
Completed
Conditions
Influenza, Human
Interventions
Drug: Placebo
Registration Number
NCT05765955
Lead Sponsor
Poolbeg Pharma plc
Brief Summary

A single center trial to evaluate the effect of POLB 001 on inflammatory responses following an intradermal LPS challenge in healthy volunteers.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
36
Inclusion Criteria
  1. Healthy male volunteers aged 18 to 55 years, inclusive.
  2. BMI in the range of 18 to 32 kg/m2 a minimum body weight of 50 kg.
  3. Fitzpatrick skin type I-III.
  4. Able to give written informed consent and willing to comply with all study-related procedures.
  5. Has the ability to communicate well with the Investigator in the Dutch language and willing to comply with the study restrictions.
Exclusion Criteria
  1. (A history of) any clinically significant medical condition or abnormalities, as judged by the investigator.
  2. History of sepsis, cardiovascular disease or malignancy.
  3. History of trauma with likely damage to the spleen or surgery to spleen.
  4. History of alcohol or drug abuse.
  5. Any clinically significant febrile illness 30 days preceding study Day 1.
  6. History of serious bleeding.
  7. Clinical evidence of significant or unstable medical illness including neurological, hematological, cardiovascular (including clinically significant arrhythmia), hepatic, pulmonary, metabolic, gastrointestinal, renal, psychiatric, endocrine, or infectious diseases or malignancies. Subjects who have had splenectomy.
  8. Previous participation in a systemic (i.v./inhaled) LPS challenge trial within a year before the first study day.
  9. Have any current and / or recurrent pathologically, clinically significant skin condition at the lower forearms (i.e., atopic dermatitis) including tattoos.
  10. Antibiotic use, operation or intervention by surgeon/dentist within one month before the first study day.
  11. Subjects who have used any prescribed or non-prescribed systemic or topical medication (including herbal remedies) within 7 days of the first dose administration, or less than 5 half-lives (whichever is longer), and during the study (except for vitamin/mineral supplements) unless, in the opinion of the Investigator, the medication will not interfere with the study procedures or compromise safety.
  12. Subjects who have received any medications, including St John's Wort, known to chronically alter drug absorption or elimination processes within 30 days of the first dose administration unless, in the opinion of the Investigator, the medication will not interfere with the study procedures or compromise safety.
  13. Any active inflammatory or infectious disease (e.g., periodontitis).
  14. Known immunodeficiency.
  15. Positive test results for Hepatitis B, Hepatitis C, HIV antibody.
  16. Subjects who consume on average more than 3 units of alcohol per day (one alcohol unit =1 beer [12 oz] =1 wine [5 oz] =1 spirits [1.5 oz]) or are unable to abstain from using alcohol during the study

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
POLB 001 70 mgPOLB 001-
POLB 001 150 mgPOLB 001-
POLB 001 30 mgPOLB 001-
PlaceboPlacebo-
Primary Outcome Measures
NameTimeMethod
Effect of intravenous LPS challenge16 days

To evaluate the effect of POLB 001 on inflammatory responses following an intravenous LPS challenge in healthy volunteers

Endpoints:

Blood

- Cytokines (IL-6, IL-8, IL-10, TNF, IL-1β) (pg/mL)

Effect of intradermal LPS challenge16 days

To evaluate the effect of POLB 001 on inflammatory responses following an intradermal LPS challenge in healthy volunteers

Endpoints:

Blister exudate analysis

- Cytokines (IL-6, IL-8, TNF, IL-1β) (pg/mL)

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Centre for Human Drug Research

🇳🇱

Leiden, Netherlands

Centre for Human Drug Research
🇳🇱Leiden, Netherlands

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