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A Combined SAD and MAD Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of IFB-088

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ClinicalTrials.gov Identifier: NCT03610334
Recruitment Status : Recruiting
First Posted : August 1, 2018
Last Update Posted : August 28, 2018
Sponsor:
Collaborators:
Qualissima
Assistance Publique des Hôpitaux de Marseille - Pharmacometry department
Stragen France
Information provided by (Responsible Party):
InFlectis BioScience

Brief Summary:
This is the first study of single and multiple doses of IFB-088 in human subjects. The current study is designed to assess in the first part, the safety, tolerability, plasma and urine pharmacokinetics (PK) of single oral doses of IFB-088 in healthy subjects (Single Ascending Doses - SAD) and in a second part safety, tolerability, plasma and urine pharmacokinetics (PK) of multiple oral doses of IFB-088 in healthy subjects (Multiple Ascending Doses - MAD)

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: IFB-088 oral capsule Drug: Placebo oral capsule Phase 1

Detailed Description:

Randomized, double blind, placebo controlled study of single ascending doses (SAD) and multiple ascending doses (MAD).

The SAD part consists of 6 cohorts of 8 healthy young male subjects, each receiving a single oral dose of IFB-088 or placebo (6 verum and 2 placebo). In each cohort, 2 subjects (1 verum and 1 placebo) will be dosed first. If the safety and tolerability results are acceptable, the 6 remaining subjects will be dosed by 2 successive groups of 3 subjects, with an adequate period between the 2 groups to detect the occurrence of any reaction or adverse events, namely at least 48H for the first cohort and at least 36H for the following cohorts. Indeed, in the first cohort (2.5 mg IFB-088 base), dosing will be in the morning only. From the second cohort, the planned daily dose will be divided into 2 doses separated by an interval of 12 hours (1 dose in the morning fasting and 1 dose in the evening 2 hours before dinner).

The MAD part consists of 3 cohorts of 8 healthy young male subjects, each receiving an oral dose divided into two doses of IFB-088 or placebo (6 verum and 2 placebo) for 14 days. In each cohort, the 2 first subjects will be dosed on Day 1 (1 verum and 1 placebo). The 6 remaining subjects will be dosed by 2 successive groups of 3 subjects with an adequate period between the groups to observe for any reaction and adverse events. This period will be of at least 5 fold the half-life of the drug (from results obtained during the SAD part) when steady state will be achieved. In each MAD cohort, the total daily dose will be divided into 2 doses separated by an interval of 12 hours.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: double-blind, randomized, placebo-controlled, combined single and multiple ascending dose of IFB-088 by successive cohorts study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Capsules used for verum or placebo (Size 5 white opaque HPMC capsule) are identical and equally-weighted
Primary Purpose: Other
Official Title: A Double-blind, Randomized, Placebo-controlled, Combined Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of IFB-088, in Healthy Volunteers
Actual Study Start Date : June 21, 2018
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : July 2019

Arm Intervention/treatment
Experimental: IFB-088

IFB-088 oral capsule:

In SAD phase: single daily dose of IFB-088 will be administered to 6 successive cohorts while increasing dose exposure.

In MAD phase: multiple doses of IFB-088 will be administered daily during 14 days to 3 succesive cohorts while increasing dose exposure.

Drug: IFB-088 oral capsule

In SAD phase: single daily dose of IFB-088 will be administered in doses ranging from 2.5mg (cohort #1 in one intake) to 60mg (cohort #2 to #6 in two intakes separated by a interval of 12 hours).

In MAD phase: multiple doses of IFB-088 will be administered daily during 14 days, in two intakes separated by an interval of 12 hours. The dose levels of the 3 cohorts will be determined after SAD phase.


Placebo Comparator: Placebo

Placebo oral capsule:

In SAD phase: single daily dose of placebo (cellulose microcrystalline) will be administered in equivalent-weight.

In MAD phase: multiple doses of placebo (cellulose microcrystalline) will be administered daily during 14 days.

Drug: Placebo oral capsule

In SAD phase: single daily dose of placebo (cellulose microcrystalline) will be administered in doses ranging (equivalent-weight) from 2.5mg (cohort #1 in one intake) to 60mg (cohort #2 to #6 in two intakes separated by a interval of 12 hours).

In MAD phase: multiple doses of placebo (cellulose microcrystalline) will be administered daily during 14 days, in two intakes separated by an interval of 12 hours.





Primary Outcome Measures :
  1. Occurrence of Adverse events (AEs) [ Time Frame: SAD & MAD phases: Continuous (Screening visit to End of study visit (7 to 14 days after last dosing) + 30 days) ]
    This safety outcome combines the measure of the number of subjects experiencing adverse events (AEs), the nature and severity of those AEs and their relationship to the study treatments.


Secondary Outcome Measures :
  1. Change in concomitant medications [ Time Frame: SAD & MAD phases: Continuous (Screening visit to End of study visit (7 to 14 days after last dosing) + 30 days) ]
    Concomitant medications (if applicable)

  2. Physical examination [ Time Frame: SAD & MAD phases: Screening; Day 2 (SAD) or Day 17 (MAD); and at End of study visit (7 to 14 days after last dosing) ]
    Full Physical examination

  3. Physiological parameters [ Time Frame: SAD & MAD phases: Screening; Day 2 (SAD) or Day 17 (MAD); and at End of study visit (7 to 14 days after last dosing) ]
    Weight and height will be combined to report BMI in kg/m^2

  4. Physical examination [ Time Frame: SAD & MAD phases: Day -1 and continuously until End of study visit (7 to 14 days after last dosing) ]
    Physical examination update

  5. Cardiovascular safety assessments [ Time Frame: From screening visit until end of study visit (7 to 14 days after last dosing) ]
    This safety outcome aims at monitoring cardiovascular functions and identify potential adverse events/reactions (clinical assessment combined with ECGs and vital signs assessments).

  6. Tympanic body temperature [ Time Frame: From screening visit until end of study visit (7 to 14 days after last dosing) ]

    Tympanic body temperature will be measured

    Timepoints expected are:

    SAD phase (cohorts 1 to 6): Screening, Day -1; Day 1 (predose, 1.5, 12, 24, 32 hours); end (7 to 14 days after last dosing)

    MAD phase: Screening; Day -1; Day 1 (predose, 1.5, 12 hours); predose at Day 2, Day 4, Day 6, Day 8, Day 10, Day 12; Day 14 (predose, 1.5, 12 hours); Day 17; end (7 to 14 days after last dosing)


  7. Laboratory evaluation: hematology [ Time Frame: From screening visit until end of study visit (7 to 14 days after last dosing) ]

    This safety outcome aims at monitoring hematology parameters and identify potential adverse events/reactions.

    Red blood cell (RBC) count, hemoglobin, hematocrit, white blood cell (WBC) count with differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), platelets, reticulocyte count will be monitored.

    Timepoints expected are:

    SAD phase: Screening; Day -1; Day 2 (24 hours); end of study visit (7 to 14 days after last dosing)

    MAD phase: Screening; Day -1; predose at Day 3, Day 6, Day 10, Day 13; Day 17; end of study visit (7 to 14 days after last dosing)


  8. Laboratory evaluation: coagulation [ Time Frame: From screening visit until end of study visit (7 to 14 days after last dosing) ]

    This safety outcome aims at monitoring coagulation parameters and identify potential adverse events/reactions.

    Activated partial thromboplastin time (APTT), international normalized ratio (INR) will be monitored.

    Timepoints expected are:

    SAD phase: Screening; Day -1; Day 2 (24 hours); end of study visit (7 to 14 days after last dosing)

    MAD phase: Screening; Day -1; predose at Day 3, Day 6, Day 10, Day ; Day 17; end of study visit (7 to 14 days after last dosing)


  9. Laboratory evaluation: Biochemestry [ Time Frame: From screening visit until end of study visit (7 to 14 days after last dosing) ]

    This safety outcome aims at monitoring blood biochemestry parameters and identify potential adverse events/reactions.

    Sodium, potassium, chloride, calcium, total bilirubin, alanine aminotransferase (ASAT), aspartate aminotransferase (ALAT), gamma-glutamyl transferase (GGT), alkaline phosphatases, total protein, albumin, urea, uric acid, bicarbonate, creatine phosphokinase (CPK), creatinine, glycaemia, lactate dehydrogenase (LDH), total cholesterol, HDL and LDL cholesterol, triglycerides will be monitored.

    Timepoints expected are:

    SAD phase: Screening; Day -1; Day 2 (24 hours); end of study visit (7 to 14 days after last dosing)

    MAD phase: Screening; Day -1; predose at Day 3, Day 6, Day 10, Day 13; Day 17; end of study visit (7 to 14 days after last dosing)


  10. Urinalysis [ Time Frame: From screening visit until end of study visit (7 to 14 days after last dosing) ]

    This safety outcome aims at monitoring urinary functions/parameters and identify potential adverse events/reactions.

    Specific gravity, pH, glucose, protein, blood, nitrites, leucocytes and ketones by dipstick.

    Results are given as "absent" or "present, not clinically significant" or "present clinically significant".

    A cytobacteriological exam will be done if abnormal results on dipstick). Beta 2 microglobulin (B2M), proteinuria and creatinuria will be also monitored.

    Timepoints expected are:

    SAD phase: Screening; Day -1; Day 1 (predose, 12, 24, 32 hours); end of study visit (7 to 14 days after last dosing)

    MAD phase: Screening; Day -1; predose at Day 1, Day 3, Day 6, Day 10, Day 13; Day 17; end of study visit (7 to 14 days after last dosing)


  11. Vigilance [ Time Frame: From screening visit until Day 14 (12 hours after last dosing) ]

    Assessment and monitoring the vigilance of healthy volunteers through the use of the Bond and Lader Visual Analogic Scale.

    Each items are scored in millimeters on a line of 10 centimeters (from 0 millimeters to 100 millimeters).

    3 sub-scale scores (Alertness, Self-contentment, Calmness) are computed by averaging their respective items.

    Each sub-scales results in a score ranged from 0 (better state) to 100 (worse state).

    Timepoints expected are:

    SAD Phase: Screening; Day 1 (predose, 1.5, 12, 32 hours)

    MAD Phase: Screening; Day 1 (predose, 1.5, 12 hours); Day 14 (predose, 1.5, 12 hours)


  12. Pharmacokinetic: Maximum observed plasma concentration (Cmax) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 72 hours after last dosing (Day 17) ]

    Plasma samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0.16, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 24, 32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0.33, 0.66, 1, 2, 3, 4, 5, 12, 12.25, 12.5, 13, 14, 16, 18, 24, 32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14 at predose, 0.33, 0.66, 1, 2, 3, 5, 12, 12.25, 12.5, 13, 14, 16, 18 hours; Day 2 (24 hours); Day 7 (predose, 1.5 hours); Day 15 (24, 28, 32 hours after Day 14); Day 16 and Day 17 (48, 72 hours after Day 14)


  13. Pharmacokinetic: Time to reach the maximum concentration in plasma (Tmax) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 72 hours after last dosing (Day 17) ]

    Plasma samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0.16, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 24, 32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0.33, 0.66, 1, 2, 3, 4, 5, 12, 12.25, 12.5, 13, 14, 16, 18, 24, 32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14 at predose, 0.33, 0.66, 1, 2, 3, 5, 12, 12.25, 12.5, 13, 14, 16, 18 hours; Day 2 (24 hours); Day 7 (predose, 1.5 hours); Day 15 (24, 28, 32 hours after Day 14); Day 16 and Day 17 (48, 72 hours after Day 14)


  14. Pharmacokinetic: Terminal elimination rate constant (Kel) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 72 hours after last dosing (Day 17) ]

    Plasma samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0.16, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 24, 32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0.33, 0.66, 1, 2, 3, 4, 5, 12, 12.25, 12.5, 13, 14, 16, 18, 24, 32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14 at predose, 0.33, 0.66, 1, 2, 3, 5, 12, 12.25, 12.5, 13, 14, 16, 18 hours; Day 2 (24 hours); Day 7 (predose, 1.5 hours); Day 15 (24, 28, 32 hours after Day 14); Day 16 and Day 17 (48, 72 hours after Day 14)


  15. Pharmacokinetic: Terminal half-life (t1/2) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 72 hours after last dosing (Day 17) ]

    Plasma samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0.16, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 24, 32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0.33, 0.66, 1, 2, 3, 4, 5, 12, 12.25, 12.5, 13, 14, 16, 18, 24, 32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14 at predose, 0.33, 0.66, 1, 2, 3, 5, 12, 12.25, 12.5, 13, 14, 16, 18 hours; Day 2 (24 hours); Day 7 (predose, 1.5 hours); Day 15 (24, 28, 32 hours after Day 14); Day 16 and Day 17 (48, 72 hours after Day 14)


  16. Pharmacokinetic: Area under plasma concentration-time curve from hour 0 to last sample with measurable plasma concentrations (AUClast) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 72 hours after last dosing (Day 17) ]

    Plasma samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0.16, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 24, 32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0.33, 0.66, 1, 2, 3, 4, 5, 12, 12.25, 12.5, 13, 14, 16, 18, 24, 32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14 at predose, 0.33, 0.66, 1, 2, 3, 5, 12, 12.25, 12.5, 13, 14, 16, 18 hours; Day 2 (24 hours); Day 7 (predose, 1.5 hours); Day 15 (24, 28, 32 hours after Day 14); Day 16 and Day 17 (48, 72 hours after Day 14)


  17. Pharmacokinetic: Area under plasma concentration-time curve from hour 0 to hour 12 (AUC0-12) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 72 hours after last dosing (Day 17) ]

    Plasma samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0.16, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 24, 32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0.33, 0.66, 1, 2, 3, 4, 5, 12, 12.25, 12.5, 13, 14, 16, 18, 24, 32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14 at predose, 0.33, 0.66, 1, 2, 3, 5, 12, 12.25, 12.5, 13, 14, 16, 18 hours; Day 2 (24 hours); Day 7 (predose, 1.5 hours); Day 15 (24, 28, 32 hours after Day 14); Day 16 and Day 17 (48, 72 hours after Day 14)


  18. Pharmacokinetic: Area under plasma concentration-time curve from hour 0 to infinity (AUC0-∞) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 72 hours after last dosing (Day 17) ]

    Plasma samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0.16, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 24, 32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0.33, 0.66, 1, 2, 3, 4, 5, 12, 12.25, 12.5, 13, 14, 16, 18, 24, 32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14 at predose, 0.33, 0.66, 1, 2, 3, 5, 12, 12.25, 12.5, 13, 14, 16, 18 hours; Day 2 (24 hours); Day 7 (predose, 1.5 hours); Day 15 (24, 28, 32 hours after Day 14); Day 16 and Day 17 (48, 72 hours after Day 14)


  19. Pharmacokinetic: Apparent volume of distribution (Vd/F) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 72 hours after last dosing (Day 17) ]

    Plasma samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0.16, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 24, 32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0.33, 0.66, 1, 2, 3, 4, 5, 12, 12.25, 12.5, 13, 14, 16, 18, 24, 32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14 at predose, 0.33, 0.66, 1, 2, 3, 5, 12, 12.25, 12.5, 13, 14, 16, 18 hours; Day 2 (24 hours); Day 7 (predose, 1.5 hours); Day 15 (24, 28, 32 hours after Day 14); Day 16 and Day 17 (48, 72 hours after Day 14)


  20. Pharmacokinetic: Apparent total body clearance (CL/F) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 72 hours after last dosing (Day 17) ]

    Plasma samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0.16, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 24, 32h

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0.33, 0.66, 1, 2, 3, 4, 5, 12, 12.25, 12.5, 13, 14, 16, 18, 24, 32h

    MAD phase (two intakes for daily administration): Day 1 and Day 14 at predose, 0.33, 0.66, 1, 2, 3, 5, 12, 12.25, 12.5, 13, 14, 16, 18h; Day 2 (24h); Day 7 (predose, 1.5 h); Day 15 (24, 28, 32h after Day 14); Day 16 and Day 17 (48, 72h after Day 14)


  21. Pharmacokinetic: Last measurable plasma concentration (Clast) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 72 hours after last dosing (Day 17) ]

    Plasma samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0.16, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 24, 32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0.33, 0.66, 1, 2, 3, 4, 5, 12, 12.25, 12.5, 13, 14, 16, 18, 24, 32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14 at predose, 0.33, 0.66, 1, 2, 3, 5, 12, 12.25, 12.5, 13, 14, 16, 18 hours; Day 2 (24 hours); Day 7 (predose, 1.5 hours); Day 15 (24, 28, 32 hours after Day 14); Day 16 and Day 17 (48, 72 hours after Day 14)


  22. Pharmacokinetic: Time to reach last measurable plasma concentration (Tlast) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 72 hours after last dosing (Day 17) ]

    Plasma samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0.16, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 24, 32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0.33, 0.66, 1, 2, 3, 4, 5, 12, 12.25, 12.5, 13, 14, 16, 18, 24, 32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14 at predose, 0.33, 0.66, 1, 2, 3, 5, 12, 12.25, 12.5, 13, 14, 16, 18 hours; Day 2 (24 hours); Day 7 (predose, 1.5 hours); Day 15 (24, 28, 32 hours after Day 14); Day 16 and Day 17 (48, 72 hours after Day 14)


  23. Pharmacokinetic: Concentration at the end of a dosing interval before the next dose administration (Ctrough) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 72 hours after last dosing (Day 17) ]

    Plasma samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0.16, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 24, 32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0.33, 0.66, 1, 2, 3, 4, 5, 12, 12.25, 12.5, 13, 14, 16, 18, 24, 32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14 at predose, 0.33, 0.66, 1, 2, 3, 5, 12, 12.25, 12.5, 13, 14, 16, 18 hours; Day 2 (24 hours); Day 7 (predose, 1.5 hours); Day 15 (24, 28, 32 hours after Day 14); Day 16 and Day 17 (48, 72 hours after Day 14)


  24. Pharmacokinetic: Maximum observed urine concentration (CmaxU) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 48 hours after last dosing (Day 16) ]

    Urine samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0-4 hours, 4-8 hours, 8-16 hours,16-32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0-4, 4-8, 8-12, 12-24, 24-32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14: predose, 0-4, 4-12, 12-24 hours; Day 6: predose, 0-4 and 4-12 hours; Day 15: 24-36, 36-48 hours after Day 14


  25. Pharmacokinetic: Time of occurrence of maximum observed urine concentration (tmaxU) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 48 hours after last dosing (Day 16) ]

    Urine samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0-4 hours, 4-8 hours, 8-16 hours,16-32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0-4, 4-8, 8-12, 12-24, 24-32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14: predose, 0-4, 4-12, 12-24 hours; Day 6: predose, 0-4 and 4-12 hours; Day 15: 24-36, 36-48 hours after Day 14


  26. Pharmacokinetic: Area under urine concentration-time curve from hour 0 to last sample with measurable urine concentrations (AUClast) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 48 hours after last dosing (Day 16) ]

    Urine samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0-4 hours, 4-8 hours, 8-16 hours,16-32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0-4, 4-8, 8-12, 12-24, 24-32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14: predose, 0-4, 4-12, 12-24 hours; Day 6: predose, 0-4 and 4-12 hours; Day 15: 24-36, 36-48 hours after Day 14


  27. Pharmacokinetic: Area under urine concentration-time curve from hour 0 to hour 12 (AUC0-12) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 48 hours after last dosing (Day 16) ]

    Urine samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0-4 hours, 4-8 hours, 8-16 hours,16-32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0-4, 4-8, 8-12, 12-24, 24-32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14: predose, 0-4, 4-12, 12-24 hours; Day 6: predose, 0-4 and 4-12 hours; Day 15: 24-36, 36-48 hours after Day 14


  28. Pharmacokinetic: Area under urine concentration-time curve from hour 0 to infinity (AUC0-∞) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 48 hours after last dosing (Day 16) ]

    Urine samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0-4 hours, 4-8 hours, 8-16 hours,16-32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0-4, 4-8, 8-12, 12-24, 24-32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14: predose, 0-4, 4-12, 12-24 hours; Day 6: predose, 0-4 and 4-12 hours; Day 15: 24-36, 36-48 hours after Day 14


  29. Pharmacokinetic: Renal clearance (CLr) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 48 hours after last dosing (Day 16) ]

    Urine samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0-4 hours, 4-8 hours, 8-16 hours,16-32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0-4, 4-8, 8-12, 12-24, 24-32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14: predose, 0-4, 4-12, 12-24 hours; Day 6: predose, 0-4 and 4-12 hours; Day 15: 24-36, 36-48 hours after Day 14


  30. Pharmacokinetic: Total amount excreted in urine (Ae) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 48 hours after last dosing (Day 16) ]

    Urine samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0-4 hours, 4-8 hours, 8-16 hours,16-32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0-4, 4-8, 8-12, 12-24, 24-32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14: predose, 0-4, 4-12, 12-24 hours; Day 6: predose, 0-4 and 4-12 hours; Day 15: 24-36, 36-48 hours after Day 14


  31. Pharmacokinetic: Percent of drug recovered in urine (Ae %dose) [ Time Frame: Starting 1 hour prior to dosing on Day 1 and until 48 hours after last dosing (Day 16) ]

    Urine samples are collected:

    SAD phase - cohort 1 (one intake for daily administration): Day 1 at predose, 0-4 hours, 4-8 hours, 8-16 hours,16-32 hours

    SAD phase - cohort 2 to 6 (two intakes for daily administration): Day 1 at predose, 0-4, 4-8, 8-12, 12-24, 24-32 hours

    MAD phase (two intakes for daily administration): Day 1 and Day 14: predose, 0-4, 4-12, 12-24 hours; Day 6: predose, 0-4 and 4-12 hours; Day 15: 24-36, 36-48 hours after Day 14



Other Outcome Measures:
  1. Exploratory [ Time Frame: SAD phase: Day 1 at predose, 1.5 hours and 24 hours ]
    Blood samples will be collected and stored in a biobank to explore potential biomarkers that remain to be identified

  2. Exploratory [ Time Frame: MAD phase: Day 1 and Day 14 at predose, 1.5 hours and 24 hours ]
    Blood samples will be collected and stored in a biobank to explore potential biomarkers that remain to be identified



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Healthy male 18 to 40 years of age inclusive, Caucasian.
  2. Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests, vital signs and ECG.
  3. AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  4. ECG (12 leads) normal (120<PR<200ms; QRS<120ms; QTcF<450ms) and/or without clinically relevant impairments as judged by investigator.
  5. Non-smoker
  6. Negative screen for alcohol and drugs of abuse at screening and admission
  7. No history of psychiatric disorders assessed by the psychological interview and the Mini International Neuropsychiatric Interview (MINI).
  8. Body mass index (BMI) between 19 and 27
  9. Subject with female partners of child bearing potential must agree to use one of the contraception methods listed in Section 6.6.1 (Contraception requirements). This criterion must be followed from the time of the first dose of study medication until the follow up visit (for female partners) and with an additional period of 90 days (for subjects themselves).
  10. Willing and able to understand and sign an approved Informed Consent Form,
  11. Able to understand the protocol and to come to the visits,
  12. Who is, in the judgement of the investigator likely to be compliant during the study,
  13. Subject registered in the VRB file (volontaires se prêtant à des recherches impliquant la personne humaine)

Exclusion Criteria:

  1. History of asthma, anaphylaxis or anaphylactoid reactions, severe allergic responses
  2. Known allergy to any component of IFB-088 oral capsule or its placebo (HPMC or cellulose microcrystalline)
  3. History of major medical, psychiatric illness or surgery which, in the judgment of the investigator, puts them 'at risk' or is likely to modify their handling of the study drug,
  4. Acute or chronic systemic disease or disorder (respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine)
  5. Renal insufficiency defined by a Glomerular Filtration Rate (GFR) < 80 ml/min/1.73m2 (according the definition of the renal function EMACHMP/EWP/225/02
  6. History of nephritic colic and/or renal calculi
  7. History of drug abuse and/or regular use of tobacco- or nicotine-containing products > 5/day within three months of the study
  8. History of alcohol consumption exceeding, (on average 21 drinks/week for men) within 6 months of the first dose of study medication
  9. Drinking excessive amounts of tea, coffee, chocolate and/or beverage containing caffeine (> 4 cups / day)
  10. Vital signs with a clinically significant abnormality at screening,
  11. ECG with a clinically significant abnormality at screening,
  12. Laboratory test values outside the clinically acceptable 'normal range' for healthy volunteers at screening,
  13. Positive HIV, Hepatitis B or Hepatitis C at screening,
  14. Positive urine drug test or positive breath alcohol test at screening or at admission to the clinical unit
  15. Any medication (including St John's Wort) within 14 days before administration, or within 5 times the elimination half-life of that drug, whichever is the longest (except paracetamol)
  16. Have used any investigational drug or participated in any clinical trial within 90 days prior to screening
  17. Unable to refrain from consumption of grapefruit or grapefruit juice within 7 days prior to the first dose of study medication
  18. Unwillingness to abstain from sexual intercourse with pregnant or lactating women or to use a condom and spermicide and another form of contraception (e.g., IUD, birth control pills taken by female partner, diaphragm with spermicide) if engaging in sexual intercourse with a woman who could become pregnant until discharge from the study and during 90 additional days
  19. Subjects unlikely to co-operate in the study, and/or poor compliance anticipated by the investigator,
  20. Subject being in the exclusion period of a previous trial,
  21. Subject having exceeded the earnings for the last 12 months,
  22. Subject who could not be contacted in case of emergency,
  23. Subject refusing to give written informed consent,
  24. Subject who has received blood or plasma derivatives in the year preceding the study,
  25. Subject who has given blood within the past 3 months or has planned to give blood or sperm within the 90 days following the study,
  26. Subject who has forfeited their freedom by administrative or legal award, or who is under guardianship or under limited judicial protection.

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): NCT03610334


Contacts
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Contact: Philippe Guedat 251 252 007 ext +33 philippeguedat@inflectisbioscience.com
Contact: Pierre Miniou 6 07 08 60 98 ext +33 pierreminiou@inflectisbioscience.com

Locations
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France
Centre d'Investigation Clinique - Centre de Pharmacologie Clinique et d'Evaluations Thérapeutiques (CIC-CPCET) Recruiting
Marseille, France, 13385
Contact: Christine Audebert, MD    491384641 ext +33    christine.audebert@ap-hm.fr   
Contact: Laurence Attolini, PhD    491388003 ext +33    laurence.attolini@ap-hm.fr   
Principal Investigator: Christine Audebert, MD         
Sub-Investigator: Marie-Noelle Lefebvre, MD         
Sub-Investigator: Frank Rouby, MD         
Sponsors and Collaborators
InFlectis BioScience
Qualissima
Assistance Publique des Hôpitaux de Marseille - Pharmacometry department
Stragen France
Investigators
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Principal Investigator: Christine Audebert, MD APHM - Centre de Pharmacolgie Clinique et d'Evaluations Thérapeutiques

Additional Information:
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Responsible Party: InFlectis BioScience
ClinicalTrials.gov Identifier: NCT03610334     History of Changes
Other Study ID Numbers: P188
2018-000443-29 ( EudraCT Number )
First Posted: August 1, 2018    Key Record Dates
Last Update Posted: August 28, 2018
Last Verified: August 2018
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

Keywords provided by InFlectis BioScience:
First-In-Human