Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 8 for:    apx001

A Drug-Drug Interaction Study of CYP3A4 Inhibition and Pan-CYP Induction on APX001

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04166669
Recruitment Status : Completed
First Posted : November 18, 2019
Last Update Posted : September 2, 2020
Sponsor:
Information provided by (Responsible Party):
Amplyx Pharmaceuticals

Brief Summary:
This is a Phase 1, open-label study to evaluate the drug-drug interaction potential of a strong CYP3A4 inhibitor (itraconazole) and a pan-CYP inducer (rifampin) on APX001 in two parallel groups of healthy subjects.

Condition or disease Intervention/treatment Phase
Fungal Infection Drug: APX001 Drug: Itraconazole Drug: Rifampin Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Fixed-Sequence, Drug-Drug Interaction Study of APX001 to Evaluate the Effects of CYP3A4 Inhibition and Pan-CYP Induction in Two Parallel Groups of Healthy Male and Female Subjects
Actual Study Start Date : November 12, 2019
Actual Primary Completion Date : March 3, 2020
Actual Study Completion Date : March 3, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions

Arm Intervention/treatment
Experimental: Cohort 1
Drugs: APX001, itraconazole
Drug: APX001
Cohort 1 Day 1: APX001 500 mg IV BID over a 3-hour infusion; Day 18: APX001 500 mg IV BID over a 3-hour infusion. Cohort 2 Day 1: APX001 1000 mg IV BID over a 3-hour infusion; Day 24: APX001 1000 mg IV BID over a 3-hour infusion.
Other Name: Fosmanogepix

Drug: Itraconazole
Cohort 1 Days 15-30: itraconazole 200 mg oral solution QD.
Other Name: Sporanox

Experimental: Cohort 2
Drugs: APX001, rifampin
Drug: APX001
Cohort 1 Day 1: APX001 500 mg IV BID over a 3-hour infusion; Day 18: APX001 500 mg IV BID over a 3-hour infusion. Cohort 2 Day 1: APX001 1000 mg IV BID over a 3-hour infusion; Day 24: APX001 1000 mg IV BID over a 3-hour infusion.
Other Name: Fosmanogepix

Drug: Rifampin
Cohort 2 Days 15-33: rifampin 600 mg oral QD.
Other Name: Rifampicin




Primary Outcome Measures :
  1. Pharmacokinetics of APX001/APX001A as measured by area under the plasma concentration-time curve (AUC) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin. [ Time Frame: 6 weeks ]
  2. Pharmacokinetics of APX001/APX001A as measured by maximum observed plasma concentration (Cmax) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin. [ Time Frame: 6 weeks ]
  3. Pharmacokinetics of APX001/APX001A as measured by time to attain maximum observed plasma concentration (Tmax) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin. [ Time Frame: 6 weeks ]
  4. Pharmacokinetics of APX001/APX001A as measured by terminal elimination rate constant (λz) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin. [ Time Frame: 6 weeks ]
  5. Pharmacokinetics of APX001/APX001A as measured by terminal elimination half-life (t1/2) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin. [ Time Frame: 6 weeks ]
  6. Pharmacokinetics of APX001/APX001A as measured by total clearance (CL) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin. [ Time Frame: 6 weeks ]
  7. Pharmacokinetics of APX001/APX001A as measured by the volume of distribution during the terminal phase (Vz) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin. [ Time Frame: 6 weeks ]

Secondary Outcome Measures :
  1. Number of subjects experiencing and frequency of occurrence of adverse events as rated by CTCAE v5.0 after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin. [ Time Frame: 6 weeks ]
  2. Occurrence and magnitude of clinical lab test values outside the normal range, clinically significant, and differing from baseline results after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin. [ Time Frame: 6 weeks ]

    The following parameters will be measured:

    • Clinical chemistry (serum quantitatively): total bilirubin, direct (conjugated) bilirubin, indirect (unconjugated) bilirubin (calculated), alkaline phosphatase, gamma-GT, ASAT, ALAT, LDH, p-amylase, lipase, CPK, creatinine, eGRF, urea, uric acid, cholesterol, triglycerides, total protein, albumin, globulin, glucose, inorganic phosphate, sodium, potassium, calcium, chloride, and bicarbonate.
    • Hematology (blood quantitatively): leukocytes, erythrocytes, hemoglobin, hematocrit, thrombocytes, partial automated absolute differentiation: lymphocytes, monocytes, eosinophils, basophils, neutrophils, MCV, MCH, and MCHC.
    • Coagulation (blood quantitatively): PT, aPTT, and fibrinogen.
    • Urinalysis (urine qualitatively): color, protein, glucose, bilirubin, urobilinogen, ketones, blood, pH, specific gravity, and leukocytes.

  3. Occurrence of abnormal vital signs after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin. [ Time Frame: 6 weeks ]
    Systolic and diastolic blood pressure and pulse will be recorded after the subject has been resting supine or semi-recumbent for at least 5 minutes. Body temperature and respiratory rate will be measured subsequently.

  4. Occurrence of abnormal, clinically significant results from 12-lead ECGs after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin. [ Time Frame: 6 weeks ]
    The following ECG parameters will be recorded: heart rate, PR interval, QRS duration, QT interval, and QTc interval (Fridericia's).

  5. Occurrence of changes in physical examinations which differ from baseline after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin. [ Time Frame: 6 weeks ]
    Physical examination will include: general appearance; skin/subcutaneous tissue; head; ears, nose, throat; neck and thyroid; thorax; lungs; cardiovascular; lymph nodes; abdomen; musculoskeletal; and neurological.



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Women must be postmenopausal or surgically sterile, or
  • Women of childbearing potential must agree to avoid pregnancy during the study and to use contraception, or abstinence, at least 2 weeks before the start of study drug administration until 3 months after the last dose of study drug.
  • Male subjects must agree to use barrier contraception, or commit to abstinence, from first Admission to the clinic until 3 months after the last dose of study drug.
  • Body mass index (BMI): 18.0 to 32.0 kg/m sq, inclusive
  • Weight: >= 50 kg
  • Screening hematology, clinical chemistry, coagulation, and urinalysis consistent with overall good health
  • Able to understand and comply with the requirements of the study, willing to return for all clinic visits, including confinement periods, and complete all study-related procedures Willing and able to provide written informed consent.

Exclusion Criteria:

  • Having any uncontrolled or active major systemic disease including, but not limited to: cardiovascular, pulmonary, ,gastrointestinal, metabolic, urogenital, neurological, immunological, psychiatric, or neoplastic disorder with metastatic potential.
  • History or presence of malignancy within the past year. Subjects who have been successfully treated with no recurrence of basal cell carcinoma of the skin or carcinoma in-situ of the cervix may be enrolled.
  • Active acute or chronic infection, including, but not limited to: upper airway infection, urinary tract infection, or skin infection within 30 days preceding entry into the study.
  • Significant and/or acute illness within 5 days prior to the first study drug administration that may impact safety assessments, in the opinion of the Investigator.
  • Participation in an investigational drug study within 60 days prior to the first study drug administration in the current study. Participation in more than 3 other drug studies in the 10 months prior to the first study drug administration in the current study.
  • Use of any prescription medication within 14 days prior to the planned first study drug administration and throughout the study (excluding female contraception).
  • Use of any non-prescription or over-the-counter medications within 7 days prior to the planned first study drug administration and throughout the study. This includes all vitamins, other herbal supplements, or remedies.
  • Taking any drug or herbal CYP3A modulator (e.g. erythromycin; St. John's Wort) within 4 weeks (or 5 half-lives, whichever is longer) or any other nutrients known to modulate CYP3A activity (e.g. grapefruit juice; Seville orange) within 2 weeks prior to the first Admission.
  • History of tobacco or any nicotine-containing product or device use within the past 3 months prior to the planned first study drug administration
  • History of alcohol or substance abuse based on Investigator's judgment, within the past 12 months prior to the planned first study drug administration
  • Concurrent social conditions (e.g. drugs-of-abuse, alcohol use of more than 24 units per week) that may potentially interfere with the subject's compliance with the protocol
  • History of clinically significant allergic drug reactions
  • Clinically significant physical examination, vital signs, laboratory safety test, or electrocardiogram (ECG) abnormalities
  • Donation or loss of more than 100 mL of blood within 60 days prior to the first study drug administration. Donation or loss of more than 1.5 liters of blood (for male subjects) or more than 1.0 liter of blood (for female subjects) in the 10 months prior to the first study drug administration in the current study.
  • Positive results on any of the following screening laboratory tests: serum pregnancy test, urine alcohol test, urine drugs-of-abuse (including cotinine), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, and human immunodeficiency virus (HIV) antibody.
  • Prior exposure to APX001
  • Known allergy to corn or corn products or any inactive components of the study drug
  • Known hypersensitivity to culprit drugs (itraconazole or rifampin).

Additional Exclusion Criteria for Cohort 2:

  • Diagnosis or suspected of having porphyria or having first-degree relatives diagnosed or suspected of having porphyria.
  • Unwilling not to use contact lenses for the duration of rifampin dosing (Day 15 to Day 33 for Cohort 2) until 7 days after the last dose of rifampin (subjects in Cohort 2 may resume wearing contact lenses on Day 40).

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): NCT04166669


Locations
Layout table for location information
Netherlands
PRA-EDS
Groningen, Netherlands
Sponsors and Collaborators
Amplyx Pharmaceuticals
Investigators
Layout table for investigator information
Principal Investigator: Sjoerd van Marle, MD PRA
Layout table for additonal information
Responsible Party: Amplyx Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04166669    
Other Study ID Numbers: APX001-107
First Posted: November 18, 2019    Key Record Dates
Last Update Posted: September 2, 2020
Last Verified: August 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Mycoses
Itraconazole
Rifampin
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers