A Study to Assess the Effect of Avacopan at Therapeutic and Supratherapeutic Doses on the QT/QTc Interval in Healthy Participants

NCT05988034 | Completed Phase 1 FDA Drug

• 1 other identifier: CL014_168
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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).

Conditions

Electrocardiography

Keywords

Complement 5a receptor (C5aR); Anti-neutrophil cytoplasmic antibody-associated vasculitis; Complement; Vasculitis

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in QTcF

  Day -1 (baseline) and up to Day 14

Secondary Outcomes (21)

• Change from Baseline in Heart Rate (HR)

  Day -1 (baseline) and 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

• 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 HR

  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

Study Arms (3)

Cohort 1: Avacopan

EXPERIMENTAL

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.

Drug: Avacopan; Drug: Placebo for moxifloxacin

Cohort 2A: Moxifloxacin/Placebo

ACTIVE COMPARATOR

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.

Drug: Moxifloxacin; Drug: Placebo for avacopan; Drug: Placebo for moxifloxacin

Cohort 2B: Placebo/Moxifloxacin

ACTIVE COMPARATOR

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.

Drug: Moxifloxacin; Drug: Placebo for avacopan; Drug: Placebo for moxifloxacin

Interventions

Avacopan DRUG

Administered orally.

Cohort 1: Avacopan

Moxifloxacin DRUG

Administered orally.

Cohort 2A: Moxifloxacin/Placebo; Cohort 2B: Placebo/Moxifloxacin

Placebo for avacopan DRUG

Administered orally.

Cohort 2A: Moxifloxacin/Placebo; Cohort 2B: Placebo/Moxifloxacin

Placebo for moxifloxacin DRUG

Administered orally.

Cohort 1: Avacopan; Cohort 2A: Moxifloxacin/Placebo; Cohort 2B: Placebo/Moxifloxacin

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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;
• Willing to communicate with an investigator and site staff and comply with all study procedures and requirements.

You may not qualify if:

• 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 -1. 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);
• Participation in another investigational drug or device study or treated with an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to Day 1;
• Received avacopan previously;
• Consumed more than 21 units of ethanol per week at any time in the 6 months prior to Day 1 (1 unit of ethanol is equivalent to 8 ounces of beer, 4 ounces of wine, or 1 ounce of spirits) or history of alcoholism and/or drug/chemical abuse within 5 years;
• Use of prescription medications (with the exception of hormone replacement therapy and hormonal birth control), including nonsteroidal anti-inflammatory drugs or sucralfate and medications known to prolong the QT/QTc interval or herbal preparations within 14 days or 5 half-lives (whichever is longer) prior to Day 1, or use of an over-the-counter medication, vitamins, or supplements (including omega-3 fish oils) within 7 days prior to Day 1;
• Use of alcohol-, caffeine-, or xanthine-containing products, Seville oranges (sour), grapefruit, or grapefruit juice, within 72 hours prior to Day 1;
• Strenuous activity (e.g., sports) from 96 hours (4 days) prior to entry into the clinical research unit (on Day -2) and throughout the study (until the final follow-up visit is conducted);

Sponsors & Collaborators

• Amgen: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

Related Publications (1)

• Miao S, Staehr P, Tai E, Darpo B, Xue H, Armas D, Webster K, Oberoi RK. A phase I thorough QT/QTc study evaluating therapeutic and supratherapeutic doses of avacopan in healthy participants. Clin Transl Sci. 2024 Jul;17(7):e13878. doi: 10.1111/cts.13878.

  PMID: 38973157 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Vasculitis

Interventions

avacopan; Moxifloxacin

Condition Hierarchy (Ancestors)

Systemic Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2023
• First Posted: August 14, 2023
• Study Start: November 8, 2019
• Primary Completion: January 22, 2020
• Study Completion: March 31, 2020
• Last Updated: August 14, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

US (1)