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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GS-248

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ClinicalTrials.gov Identifier: NCT04036227
Recruitment Status : Recruiting
First Posted : July 29, 2019
Last Update Posted : July 29, 2019
Sponsor:
Collaborator:
CTC Clinical Trial Consultants
Information provided by (Responsible Party):
Gesynta Pharma AB

Brief Summary:
This is a First in Human (FIH), double-blinded, parallel-group, randomised, placebo-controlled study designed to evaluate the safety, tolerability, PK and PD of single and multiple ascending oral doses of GS-248 in healthy subjects.

Condition or disease Intervention/treatment Phase
Healthy Drug: GS-248 Drug: Placebo Phase 1

Detailed Description:

Part I (SAD); In the SAD part of the study, single oral doses of GS-248 will be administered in 6 sequential cohorts, each consisting of 8 subjects randomised to receive either GS 248 or placebo in a 3:1 ratio. The first 2 subjects in each cohort will be dosed in a sentinel fashion; 1 subject will receive GS-248 and the other will receive placebo as randomised. The subjects will be carefully monitored by clinical staff during and after dosing. Vital signs and ECG will be checked at regular intervals.

Part II (MAD); The MAD part of the study will explore multiple ascending dosing of GS-248 administered for 10 days. The proposed starting dose is 25 mg/day. However, the starting dose as well as subsequent dose levels may be adjusted based on safety and PK evaluation in previous cohorts. GS-248 will be administered in 4 sequential cohorts, each of 8 subjects randomised to receive either GS 248 or placebo in a 3:1 ratio. The subjects will be carefully monitored by clinical staff during and after dosing. Vital signs and ECG will be checked at regular intervals.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Part I (SAD) Within each cohort, subjects will be randomised in a 3:1 ratio to receive either GS 248 (n=6) or placebo (n=2) in a blinded fashion.

Part II (MAD) Within each cohort, subjects will be randomised in a 3:1 ratio to receive GS-248 (n=6) or placebo (n=2) in a blinded fashion.

Masking: Double (Participant, Investigator)
Masking Description:

The study will be conducted in double-blind fashion and the allocation of treatments will not be disclosed until clean file has been declared and the database has been locked.

GS-248 and the placebo are identical in appearance, taste and smell.

Primary Purpose: Treatment
Official Title: A Phase I, Placebo-controlled, Double-blind, First-in-human Study to Investigate Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of GS-248 Solution in Healthy Subjects and Patients With Systemic Sclerosis (SSc)
Actual Study Start Date : July 4, 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: GS-248

Part I (SAD): Single doses of 1 mg, 5 mg, 25 mg, 75 mg, 225 mg and 450 mg (planned doses)

Part II (MAD): Multiple ascending doses for 10 days in four cohorts with planned doses of 25 mg, 75 mg, 225 mg and 450 mg. The doses will be finally selected based on results from Part I.

Drug: GS-248
GS-248 oral solution

Placebo Comparator: Placebo
Matching placebo oral solution
Drug: Placebo
Placebo oral solution with the same composition to match active drug




Primary Outcome Measures :
  1. Number of treatment related adverse event, including abnormal laboratory events [ Time Frame: SAD: From Pre-dose to Day 8; MAD: From Pre-dose to Day 19 ]
    Frequency, severity and seriousness of adverse events (AEs) including physical examination, safety laboratory parameters, vitals signs, body temperature and ECGs will be analyzed


Secondary Outcome Measures :
  1. Cmax: [ Time Frame: SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 24 hours post first and last dose ]
    maximum plasma concentration

  2. Tmax: [ Time Frame: SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 24 hours post first and last dose ]
    time to Cmax

  3. T½: [ Time Frame: SAD: From pre-dose up to 48 hours post-dose; MAD: From pre-dose to 24 hours post first and last dose ]
    terminal half-life

  4. AUC0-t: [ Time Frame: SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 24 hours post first and last dose ]
    area under the curve from time 0 to time t

  5. CL/F: [ Time Frame: SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 24 hours post first and last dose ]
    apparent total body clearance following extravascular administration

  6. Vz/F: [ Time Frame: SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 24 hours post first and last dose ]
    apparent volume of distribution following extravascular administration


Other Outcome Measures:
  1. mPGES-1 activity [ Time Frame: From pre-dose to 24 hours post-dose ]
    Ex vivo determination of mPGES-1 activity (PGE2 levels) in a Whole Blood Assay

  2. Plasma and urine concentrations GS-248 metabolites [ Time Frame: SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 24 hours post first and last dose ]
    Collection of plasma and urine for analysis of metabolites after single and multiple dosing with GS-248



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Willing and able to give written informed consent for participation in the study.
  2. Male and female healthy subjects aged 18-70 years inclusive (Part I [SAD]) and 40-75 years inclusive (Part II [MAD])
  3. Women of child bearing potential must practice abstinence or must agree to use a highly effective method of contraception with a failure rate of < 1% to prevent pregnancy from at least 4 weeks prior to dose to 4 weeks after last dose. Their male partner must agree to use a condom during the same time frame. Women of non-childbearing potential are defined as pre-menopausal females who are sterilised or post-menopausal defined as 12 months of amenorrhea.

    Male subjects must be willing to use condom or be vasectomised or practice sexual abstinence. Their female partner of child-bearing potential must use contraceptive methods with a failure rate of < 1% to prevent pregnancy (see above).

  4. Body mass index (BMI) ≥ 19 and ≤ 30 kg/m2.
  5. Subjects must be in good health as determined by medical history, physical examination, vital signs, 12-lead ECG and clinical laboratory assessments at the time of screening, as judged by the Investigator.

Exclusion Criteria:

  1. Known allergy to any components of the GS-248 formulation.
  2. Females who are breast feeding or plan to be pregnant.
  3. Positive serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) at screening and within 24 h prior to the first administration of IMP.
  4. Use of corticosteroids (inhaled and systemic), NSAIDs (including e.g. coxibs and aspirin), antacids, PPIs or any medication that changes gastric pH within 2 weeks prior to the (first) administration of IMP.
  5. Regular use of any prescribed or non-prescribed medication including analgesics, herbal remedies, vitamins and minerals within 2 weeks prior to the (first) administration of IMP, except hormonal contraception and occasional intake of paracetamol (maximum 2000 mg/day; and not exceeding 3000 mg/week) and nasal decongestants without cortisone, antihistamine or anticholinergics for a maximum of 10 days, at the discretion of the Investigator.
  6. Inherited or acquired disorders of platelet function, bleeding or coagulation.
  7. Presence of any clinically relevant acute or chronic disease that could interfere with the subject's safety during the clinical study or expose the subject to undue risk.
  8. After 10 minutes supine rest at the time of screening, any vital signs values outside the following ranges:

    • Systolic blood pressure <90 or >140 mmHg, or
    • Diastolic blood pressure <50 or >90 mmHg, or
    • Pulse <40 or >90 bpm
  9. Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCVAb) or human immunodeficiency virus (HIV) 1 and/or 2 antibodies at screening.
  10. Presence or history of drug and/or alcohol abuse and/or excessive intake of alcohol and/or history, or current use, of anabolic steroids, as judged by the Investigator.
  11. Any positive result for drug abuse and/or alcohol at screening or on admission to the unit prior to administration of the IMP.
  12. Participation in another clinical study with an experimental drug within 3 months before the administration of IMP.
  13. Consumption of grapefruit or grapefruit juice within 14 days of study drug administration.
  14. Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP.
  15. Malignancy within the past 5 years with the exception of in situ removal of basal cell carcinoma or resected benign colonic polyps.
  16. Any planned major surgery within the duration of the study.
  17. Prolonged QTcF (>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator.
  18. Current smokers or users of nicotine products. Irregular use of nicotine (e.g. smoking, snuffing, chewing tobacco) less than 3 times per week is allowed before screening visit.
  19. Regular excessive caffeine consumption defined by a daily intake of >5 cups of caffeine containing beverages.
  20. Intake of xanthine and/or taurine containing energy drinks within 2 days prior to screening.
  21. Plasma donation within one month of screening or blood donation (or corresponding blood loss) during the three months prior to screening.
  22. Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04036227


Contacts
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Contact: Folke Sjöberg, MD +46 (0)70 557 1820 folke.sjoberg@ctc-ab.se
Contact: Göran Tornling, MD +46 (0)73 096 3131 goran.tornling@gesynta.se

Locations
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Sweden
CTC Clinical Trial Consultants AB Recruiting
Uppsala, Sweden, SE-75237
Contact: Anna Stendahl    +46 (0)73 866 48 87    anna.stendahl@ctc-ab.se   
Contact: Måns Jergil    +46 (0)70 330 3946    mans.jergil@ctc-ab.se   
Sponsors and Collaborators
Gesynta Pharma AB
CTC Clinical Trial Consultants
Investigators
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Principal Investigator: Folke Sjöberg, MD CTC Clinical Trial Consultants AB

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Responsible Party: Gesynta Pharma AB
ClinicalTrials.gov Identifier: NCT04036227     History of Changes
Other Study ID Numbers: GS-1001
First Posted: July 29, 2019    Key Record Dates
Last Update Posted: July 29, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pharmaceutical Solutions