Effect of Repeated Oral Doses of Avacopan on the Pharmacokinetics (PK) of a Single Dose of Simvastatin

NCT06207682 | Completed Phase 1 FDA Drug

• 1 other identifier: CL020_168
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this clinical study is to evaluate the effect of repeated oral doses of avacopan (30 mg and 60 mg twice daily approximately 12 hours apart \[BID\]) given under fed conditions on the PK of a single dose of simvastatin (40 mg) in healthy volunteers.

Conditions

Healthy Volunteers

Keywords

Avacopan; CCX168; Simvastatin

Outcome Measures

Primary Outcomes (6)

• Maximum Observed Plasma Concentration (Cmax) of Simvastatin

  Up to Day 12

• Cmax of β-hydroxy-simvastatin Acid

  Up to Day 12

• Area Under the Plasma Concentration-time Curve from Time 0 to the Time Point of Last Quantifiable Plasma Concentration (AUClast) of Simvastatin

  Up to Day 12

• AUClast of β-hydroxy-simvastatin Acid

  Up to Day 12

• Area Under the Plasma Concentration-time Curve from Time 0 to Infinity (AUCinf) of Simvastatin

  Up to Day 12

• AUCinf of β-hydroxy-simvastatin Acid

  Up to Day 12

Secondary Outcomes (5)

• Number of Participants Experiencing Adverse Events

  Up to Day 26

• Cmax of Avacopan

  Up to Day 12

• Cmax of Avacopan Metabolite M1

  Up to Day 12

• Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUCtau) of Avacopan

  Up to Day 12

• AUCtau of Avacopan Metabolite M1

  Up to Day 12

Study Arms (2)

Arm 1: Avacopan and Simvastatin

EXPERIMENTAL

A single dose of 40 mg simvastatin will be given orally in the morning on Day 1 and Day 10. The Day 10 dose of simvastatin will be co-administered with the morning dose of avacopan. On Days 3 through 11, avacopan will be given orally at 30 mg BID.

Drug: Avacopan; Drug: Simvastatin

Arm 2: Avacopan and Simvastatin

EXPERIMENTAL

A single dose of 40 mg simvastatin will be given orally in the morning on Day 1 and Day 10. The Day 10 dose of simvastatin will be co-administered with the morning dose of avacopan. On Days 3 through 11, avacopan will be given orally at 60 mg BID.

Drug: Avacopan; Drug: Simvastatin

Interventions

Avacopan DRUG

Orally via capsules

Also known as: CCX168

Arm 1: Avacopan and Simvastatin; Arm 2: Avacopan and Simvastatin

Simvastatin DRUG

Orally via tablets

Arm 1: Avacopan and Simvastatin; Arm 2: Avacopan and Simvastatin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female adults, 18-55 years of age, inclusive.
• Body mass index (BMI) is 18.5 to 29.9 kg/m\^2.
• Negative result of the human immunodeficiency virus (HIV) screen, the hepatitis B screen, the hepatitis C screen, and the QuantiFERON®-TB Gold test.
• A female participant is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented bilateral tubal ligation, bilateral salpingectomy, bilateral oophorectomy (removal of the ovaries) or hysterectomy; hysteroscopic sterilization, or post-menopausal defined as ≥12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \[FSH\] in the post-menopausal range is confirmatory). Documented verbal history from the participant is acceptable for all of the criteria stipulated above.
• Child-bearing potential and agrees to use effective contraception methods from the signing of informed consent until 120 days after the last dose of study treatment.
• Lactating but willing to stop breast feeding prior to the first dose of study treatment until 120 days after the last dose of study treatment.
• Female participants must agree not to donate ova starting at Screening and for 120 days after the final study drug administration.
• Male participants must agree to use highly effective contraception methods. This criterion must be followed from the time of the first dose of study treatment until 120 days after the last dose of study treatment.
• Male participants must agree not to donate sperm starting from the time of the first dose of study treatment and for 120 days after the final study drug administration

You may not qualify if:

• Willing and able to provide written Informed Consent and to comply with the requirements of the study protocol.
• Women who are pregnant, breastfeeding, or have a positive serum pregnancy test at Screening or on Study Day -1 or women who desire to begin a family or breastfeed during the full length of the study.
• Expected requirement for use of any medication (with the exception of continued use by female participants of hormonal contraceptives in accordance with a regimen that has been stable for at least the three months prior to Screening and post-menopausal females using estrogen replacement therapy) from Screening through the end of the study.
• History within the 60 days prior to the first administration of Investigational Product (IP) of use of cannabis, tobacco and/or nicotine-containing products.
• History of drug abuse (either illicit or prescription) within two years prior to first administration of IP.
• History of alcohol abuse at any time in the past five years from Screening.
• History or presence of any form of cancer within the 5 years prior to screening, with the exception of excised basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ such as cervical or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis.
• History or presence of any medical condition or disease or laboratory abnormality which, in the opinion of the Investigator, may place the participant at unacceptable risk for study participation.
• Donated or lost more than 50 mL of blood or blood products within 56 days prior to screening, or donated plasma within 7 days of randomization.
• Hemoglobin less than the lower limit of normal or recent history (6 months prior to first dose) of iron deficient anemia.
• Received a live vaccine or a vaccine for coronavirus 19 disease (COVID-19) within 4 weeks prior to Screening
• Current or recent COVID-19 infection defined as:
• positive result of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-V2) test at screening or Day-1, or
• symptomatic COVID-19 infection within 30 days prior to Day-1, or
• continuing COVID-19 long haul symptomatology regardless of when the initial COVID-19 infection occurred

Sponsors & Collaborators

• Amgen: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

Related Publications (1)

• Miao S, Bekker P, Armas D, Lor M, Han Y, Webster K, Trivedi A. Pharmacokinetic Evaluation of the CYP3A4 and CYP2C9 Drug-Drug Interaction of Avacopan in 2 Open-Label Studies in Healthy Participants. Clin Pharmacol Drug Dev. 2024 May;13(5):517-533. doi: 10.1002/cpdd.1389. Epub 2024 Feb 29.

  PMID: 38423992 DERIVED

MeSH Terms

Interventions

avacopan; Simvastatin

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2024
• First Posted: January 17, 2024
• Study Start: June 28, 2022
• Primary Completion: August 11, 2022
• Study Completion: August 11, 2022
• Last Updated: January 17, 2024

Record last verified: 2023-12

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)