Clinical Trials/NCT05988034

NCT05988034

Completed

Phase 1

A Multiple-dose, Randomized, Double-blind, Placebo-controlled, Active-Comparator, Parallel Study to Investigate the Effect of Avacopan at Therapeutic and Supratherapeutic Doses on the QT/QTc Interval in Healthy Subjects

Amgen1 site in 1 country58 target enrollmentNovember 8, 2019

ConditionsElectrocardiography

InterventionsAvacopan Placebo for moxifloxacin Moxifloxacin Placebo for avacopan

DrugsAvacopan Moxifloxacin Placebo for avacopan Placebo for moxifloxacin

Overview

Phase: Phase 1
Intervention: Avacopan
Conditions: Electrocardiography
Sponsor: Amgen
Enrollment: 58
Locations: 1
Primary Endpoint: Change from Baseline in QTcF
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The primary objective of this study is to evaluate the effects of therapeutic and supratherapeutic doses of avacopan on the heart rate corrected QT interval, using Fridericia's formula (QTcF).

Registry

clinicaltrials.gov

Start Date

November 8, 2019

End Date

March 31, 2020

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Amgen

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Be able to verbalize understanding of consent form and able to provide written informed consent;
•Healthy male or female: No known history of a clinically significant medical diagnosis in the opinion of the Investigator and is not receiving prescription medication except birth control therapies; this includes but is not limited to no history of heart or lung disease (including latent tuberculosis), high blood pressure, history of any cardiac or endocrine disease (including thyroid disease and diabetes); appendectomy and cholecystectomy are allowed;
•Aged ≥18 and ≤60 years at the time of screening;
•Body mass index ≥18.0 and ≤30.0 kg/m\^2, and body weight of ≥50 kg, at screening and Day -2;
•Non- or ex-smoker; an ex-smoker is defined as someone who completely stopped using nicotine products for at least 180 days prior to the first study drug administration;
•A female participant meeting 1 of the following criteria: (1) female participants of child-bearing potential using adequate contraception during and for at least 90 days after any administration of study medication; or (2) physiological postmenopausal status, defined as the following: absence of menses for at least 1 year prior to the first study drug administration (not due to amenorrhea secondary to lactation); and follicle stimulating hormone (FSH) levels ≥40 mIU/mL at screening; or (3) surgical postmenopausal status, defined as the following: bilateral oophorectomy; and absence of menses for at least 90 days prior to the first study drug administration; and FSH levels ≥40 mIU/mL at screening; or (4) surgical sterilization including tubal ligation, salpingectomy and hysterectomy. If the postmenopausal participant has an FSH of \<40 mIU/mL, but meets the above criteria in either (1), (2), (3) or (4) (for all aspects other than FSH levels) as well as all the other inclusion criteria, the participant may be included in the study if the estradiol serum level measured at screening is equal to or below 150 pmol/L. If male, non-vasectomized participants with female partners of child-bearing potential must agree to use contraception and agree not to donate sperm during the study period and for 90 days after the last study drug administration;
•Willing to communicate with an investigator and site staff and comply with all study procedures and requirements.

Exclusion Criteria

•An uninterpretable or abnormal screening electrocardiogram (ECG) indicating a second- or third-degree atrioventricular block, or one or more of the following: QRS interval \>110 msec; QTcF \>450 msec; PR interval \>200 msec; HR \<40 bpm; or any rhythm other than sinus rhythm that is interpreted an investigator to be clinically significant;
•History of risk factors for torsades de pointes, including unexplained syncope, known long QT syndrome, heart failure, myocardial infarction, angina, or clinically significant abnormal laboratory assessments including hypokalemia, hypercalcemia, or hypomagnesemia. Participants will also be excluded if there is a family history of long QT syndrome or Brugada syndrome;
•A sustained supine systolic blood pressure \>150 mm Hg or \<90 mm Hg or a supine diastolic blood pressure \>95 mm Hg or \<50 mm Hg at screening or on Day -
•Blood pressure may be retested more than once in the supine position. The blood pressure abnormality is considered sustained if either the systolic or the diastolic pressure values are outside the stated limits after 3 assessments and the participant may not be randomized;
•A resting HR of \<40 bpm or \>100 bpm when vital signs are measured at screening or on Day -1;
•Unstable cardiovascular disease, including recent myocardial infarction or cardiac arrhythmia;
•History of acquired immunodeficiency syndrome or positive test results for human immunodeficiency virus, hepatitis C virus antibody, or hepatitis B surface antigen at screening;
•Positive urine drug or alcohol screen at screening or on Day -2 (admission);
•Clinically significant illness, including viral syndromes within 3 weeks prior to Day 1;
•Women who are pregnant according to a serum pregnancy test (or planning to become pregnant within the next 6 months) or currently breastfeeding, at screening or according to a urine pregnancy test on Day -2 (admission);

Arms & Interventions

Cohort 1: Avacopan

Participants will be randomized to receive multiple doses of avacopan orally twice daily (BID): 30 mg for 7 days and 100 mg for 7 days, for a total of 14 dosing days, and placebo for moxifloxacin on Days 1 and 15.

Intervention: Avacopan

Cohort 1: Avacopan

Intervention: Placebo for moxifloxacin

Cohort 2A: Moxifloxacin/Placebo

Participants will be randomized to receive moxifloxacin 400 mg orally on Day 1, placebo for avacopan BID on Days 1 to 14, and placebo for moxifloxacin on Day 15.

Intervention: Moxifloxacin

Cohort 2A: Moxifloxacin/Placebo

Participants will be randomized to receive moxifloxacin 400 mg orally on Day 1, placebo for avacopan BID on Days 1 to 14, and placebo for moxifloxacin on Day 15.

Intervention: Placebo for avacopan

Cohort 2A: Moxifloxacin/Placebo

Participants will be randomized to receive moxifloxacin 400 mg orally on Day 1, placebo for avacopan BID on Days 1 to 14, and placebo for moxifloxacin on Day 15.

Intervention: Placebo for moxifloxacin

Cohort 2B: Placebo/Moxifloxacin

Participants will be randomized to receive placebo for moxifloxacin orally on Day 1, placebo for avacopan BID on Days 1 to 14, and moxifloxacin 400 mg orally on Day 15.

Intervention: Moxifloxacin

Cohort 2B: Placebo/Moxifloxacin

Participants will be randomized to receive placebo for moxifloxacin orally on Day 1, placebo for avacopan BID on Days 1 to 14, and moxifloxacin 400 mg orally on Day 15.

Intervention: Placebo for avacopan

Cohort 2B: Placebo/Moxifloxacin

Participants will be randomized to receive placebo for moxifloxacin orally on Day 1, placebo for avacopan BID on Days 1 to 14, and moxifloxacin 400 mg orally on Day 15.

Intervention: Placebo for moxifloxacin

Outcomes

Primary Outcomes

Change from Baseline in QTcF

Time Frame: Day -1 (baseline) and up to Day 14

Secondary Outcomes

Change from Baseline in Complex Between Q and S Wave (QRS Interval)(Day -1 (baseline) and Days 1, 7, and 14)
Placebo-corrected Change from Baseline in QTcF(Day -1 (baseline) and Days 1, 7, and 14)
Placebo-corrected Change from Baseline in QRS Interval(Day -1 (baseline) and Days 1, 7, and 14)
Change from Baseline in Heart Rate (HR)(Day -1 (baseline) and Days 1, 7, and 14)
Number of Participants with Categorical Increases in QTcF from Baseline(Day -1 (baseline) and Days 1, 7, and 14)
Time of Cmax (Tmax) of Avacopan(Up to Day 14)
Cmax of Avacopan Metabolite M1(Up to Day 14)
Number of Participants with Categorical Increases in PR Interval from Baseline(Day -1 (baseline) and Days 1, 7, and 14)
Number of Participants with Categorical Decreases in HR from Baseline(Day -1 (baseline) and Days 1, 7, and 14)
Change from Baseline in the Number of U-waves(Day -1 (baseline) and Days 1, 7, and 14)
AUC0-6h of Avacopan Metabolite M1(Up to Hour 6 post-dose on Days 1, 7, and 14)
AUC From Time 0 to 12 Hours (AUC0-12h) of Avacopan(Up to Hour 12 post-dose on Days 1, 7, and 14)
Placebo-corrected Change from Baseline in HR(Day -1 (baseline) and Days 1, 7, and 14)
Number of Participants with Categorical Increases in QRS Interval from Baseline(Day -1 (baseline) and Days 1, 7, and 14)
Tmax of Avacopan Metabolite M1(Up to Day 14)
Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to 6 Hours (AUC0-6h) of Avacopan(Up to Hour 6 post-dose on Days 1, 7, and 14)
AUC0-12h of Avacopan Metabolite M1(Up to Hour 12 post-dose on Days 1, 7, and 14)
Change from Baseline in Time Between P and R Wave (PR Interval)(Day -1 (baseline) and Days 1, 7, and 14)
Placebo-corrected Change from Baseline in PR Interval(Day -1 (baseline) and Days 1, 7, and 14)
Change from Baseline in the Number of T-wave Morphology Findings(Day -1 (baseline) and Days 1, 7, and 14)
Maximum Observed Plasma Concentration (Cmax) of Avacopan(Up to Day 14)