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Multiple Ascending Dose Phase I Study in Order to Define Lanifibranor (IVA337) Supra-thjerapeutic Dose (MAD)

I

Inventiva Pharma

Status and phase

Completed
Phase 1

Conditions

Healthy Subjects

Treatments

Drug: Placebo
Drug: Moxifloxacin
Drug: Lanifibranor

Study type

Interventional

Funder types

Industry

Identifiers

NCT03866369
2018-003822-99 (EudraCT Number)
337HVPK18007

Details and patient eligibility

About

The study will be a double-blind, randomized, placebo-controlled, multiple ascending dose study with lanifibranor. The study will consist of up to 3 cohorts of 12 subjects each; therefore, approximately 36 subjects will be included in this study.

Full description

All subject will receive first a single dose of 400 mg moxifloxacin, under open-label fasting conditions at Day -8 (assay sensitivity).

Following, all subjects also will receive a dose of placebo under open-label fasting conditions at D-1.

In the morning of Day 1, subjects will be randomized to either the investigational medicinal product (IMP) or placebo (3:1). The treatment phase last 14 days and the end of study visit will occurs within 5 to 9 days after the last dose of IMP or placebo (or at early termination)

A staggered dose approach will be applied within each subjects cohort with 48 hours of delay between subcohorts.

A sefty review committe (SRC) will review after each cohorts all available safety and PK data under blinded conditions and conclude the safety and tolerability of the dose level before proceeding to the next dose level.

Enrollment

36 patients

Sex

Male

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

Main inclusion Criteria:

Subject voluntarily agrees to participate in this study and signs an IEC-approved informed consent prior to performing any of the Screening Visit procedures.

  1. Males between 18 to 55 years of age (inclusive) 3. Nonsmokers (or other nicotine use) as determined by history (no nicotine use over the past 3 months) and by urine cotinine concentration (< 500 ng/mL) at the Screening Visit and admission.

  2. Body mass index (BMI) between 18.0 and 29.9 kg/m2 (inclusive) at the Screening Visit.

  3. Healthy with no clinically relevant deviation or finding in medical history, physical examinations, vital signs or 12-lead ECGs at the Screening Visit or admission, as applicable. Clinical laboratory values at the Screening Visit or admission should be within normal limits or judged not clinically significant as determined by the Investigator and with liver values such as:

  • Alanine aminotransferase (ALT) ≤ 1.1 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) ≤ 1.2 × ULN
  • Gamma-glutamyltransferase (GGT) ≤ 1.5 × ULN
  • Alkaline phosphatase (ALP) ≤ 1.5 × ULN

Main exclusion Criteria:

  1. History or evidence of any relevant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic (e.g., diabetes), urologic, pulmonary, neurologic, psychiatric, dermatologic, renal (e.g., renal insufficiency), and/or other major disease or malignancy (e.g., bladder cancer) or present infectious disease as judged by the Investigator.

  2. Subject has any surgical or medical condition that would interfere with the absorption, distribution, metabolism or excretion of drugs, or which may jeopardize the subject in case of participation in the study.

    1. Inflammatory bowel disease, peptic ulcers, gastrointestinal including rectal bleeding.

    2. Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection.

    3. Pancreatic injury or pancreatitis within 12 months prior to Screening.

    4. Liver disease or liver injury as indicated by abnormally increased liver function tests. ALT, AST, GGT, ALP, and serum bilirubin will be tested at Screening.

      • Any single parameter of ALT, AST, GGT, or ALP must not exceed 1.1 x ULN and ≥ 1.2 x ULN total bilirubin.
      • Any elevation above ULN of more than one parameter of ALT, AST, GGT, ALP, or serum bilirubin will exclude a subject from participation in the study.

      If necessary, laboratory testing may be repeated on one occasion (as soon as possible) prior to randomization, to rule out any laboratory error.

    5. History or presence of impaired renal function as indicated by clinically significantly abnormal creatinine or blood urea nitrogen and/or urea values, or abnormal urinary constituents (e.g. albuminuria).

    6. Evidence of urinary obstruction or difficulty in voiding

    7. History of immunodeficiency diseases.

    8. Blood levels of sodium, potassium, calcium, or magnesium outside of laboratory normal range at Screening and baseline.

    9. TSH outside of laboratory normal range at Screening.

  3. Subject has any concurrent disease or condition that, in the opinion of the Principal Investigator, would make the subject unsuitable for participation in the clinical study.

  4. Subject has a pulse < 50 beats per minute (bpm) or > 90 bpm; systolic BP < 90 mmHg or > 140 mmHg; diastolic BP < 50 mmHg or > 90 mmHg at the Screening Visit. One re-test is allowed, if (a) test result(s) is outside these limits.

  5. Abnormal 12-lead ECG at the Screening Visit or admission, including:

    • Uncorrected QT interval ≥ 500 msec
    • QTcF > 450 msec
    • QRS interval >120 msec
    • PR interval >220 msec
    • Second or third-degree atrio-ventricular block
    • Any rhythm other than sinus rhythm, which is interpreted by the Investigator to be clinically significant
  6. Subject has clinically significant conduction disorders, significant arrhythmia or a known risk from medical history to not respond to moxifloxacin.

  7. Subject has a history of additional risk factors for "Torsades de Pointe" (e.g., heart failure, hypokalemia [below the lower limit of normal], family history of Long QT Syndrome).

  8. Family history of QTc prolongation or of unexplainable sudden death at < 50 years of age.

  9. Any contraindication or reasons for precautionary use of moxifloxacin such as:

    • History of allergy/phototoxicity with quinolone group of drugs in the last year prior to Screening.
    • History of peripheral neuropathy.
    • History of tendinitis, tendon rupture, or clinically significant tendon injury.
    • Risk factor associated with psychiatric reactions.
    • History of seizure disorders or disease which can lower seizure threshold.
  10. Subject has a history or family history of G6PD or any other congenital hemolytic anemias.

  11. Subject has history of illicit drug abuse.

  12. Subject has a history of drinking > 168 g pure alcohol per week (10 g pure alcohol = 259 mL of beer [5%] or 35 mL of spirits [35%] or 100 mL of wine [12%]) within 2 years prior to the first admission to the clinical unit.

  13. Subject has positive test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis C antibody (anti-HCV) or human immunodeficiency virus (HIV) antibodies (types 1 and 2) at the Screening Visit.

  14. Subject has positive alcohol test at the Screening Visit or admission.

  15. Subject has positive urine drug test (e.g., cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids) at the Screening Visit or admission.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Sequential Assignment

Masking

Quadruple Blind

36 participants in 2 patient groups, including a placebo group

Experimental
Experimental group
Description:
IMP Under investigation
Treatment:
Drug: Moxifloxacin
Drug: Lanifibranor
Drug: Placebo
Drug: Placebo
Placebo to Match
Placebo Comparator group
Treatment:
Drug: Moxifloxacin
Drug: Placebo
Drug: Placebo

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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