A Study to Assess the Mass Balance Recovery (Absorption, Distribution, Metabolism and Excretion) of [14C]CCX168 in Healthy Participants

An Open-Label, Phase 1 Study in Healthy Volunteers to Evaluate the Mass Balance Recovery and Metabolic Disposition of a Single Oral Dose of [14C]CCX168

The primary objective of this study is to perform mass balance following a single oral dose of [14C]CCX168 in healthy adult male participants.

Study Overview

• Status: Completed
• Conditions: Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis
• Intervention / Treatment: Drug: [14C]CCX168

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Covance Clinical Research Unit, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Males, aged 18-55 years inclusive, who are in generally good health, whose body mass index is 19.0 to 30.0 kg/m^2 inclusive;
• Willing and able to give written Informed Consent and to comply with the requirements of the study protocol;
• Negative result of the human immunodeficiency virus screen, the hepatitis B screen, and the hepatitis C screen;
• Judged to be healthy by the Investigator, based on medical history, physical examination (including electrocardiogram), and clinical laboratory assessments. Participants with clinical laboratory values that are outside of normal limits and/or with other abnormal clinical findings that are judged by the Investigator not to be of clinical significance may be entered into the study;
• Male participants with partners of childbearing potential may participate if adequate contraception is used during, and for 90 days after, any administration of study medication;
• Males must refrain from sperm donation for 90 days following completion of the study;
• Participants must have regular (at least once per day) bowel movements.

Exclusion Criteria:

• Participated in any studies where any radiolabeled drug was administered in the year prior to enrollment;
• Received a diagnostic or therapeutic radiation dose (such as a barium meal, serial x-ray scan, or computed tomography scan) within 1 year of enrollment or are currently employed in a job requiring radiation exposure monitoring;
• Expected requirement for use of any medication during the study period;
• For at least 3 days prior to enrollment and throughout the blood sample collection period, participants will not be allowed to eat any food or drink any beverage containing alcohol, caffeine, grapefruit, grapefruit juice, Seville oranges, or charbroiled meat;
• History within the three months prior to study entry of use of tobacco and/or nicotine containing products;
• History within one year prior to study entry of illicit drug use;
• History of alcohol abuse at any time in the past;
• History of any form of cancer;
• History or presence of any medical condition or disease which, in the opinion of the Investigator, may place the participant at unacceptable risk for study participation;
• Donated or lost more than 350 mL of blood or blood products within 56 days prior to screening, or donated plasma within 7 days of dosing;
• Participant's hemoglobin less than 12 g/dL, confirmed by repeat measurement;
• Participated in any clinical study of an investigational product within 30 days prior to dosing;
• Participant has any evidence of hepatic disease; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, or bilirubin greater than the upper limit of normal, unless considered not clinically significant by the Investigator;
• Participant's white blood cell count is below the lower limit of normal at Screening or Check-in (Day -1), confirmed by repeat measurement;
• Participant has any evidence of renal impairment; serum creatinine greater than the upper limit of normal, unless considered not clinically significant by the investigator;
• Participant's urine tested positive at Screening and/or on Study Day -1 for any of the following: opioids, amphetamines and methamphetamines, cannabinoids, benzodiazepines, barbiturates, cocaine, cotinine, ecstasy, methadone, phencyclidine, tricyclic antidepressants, or alcohol Breathalyzer test allowed for alcohol).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [14C]CCX168; Participants will receive a single oral dose of [14C]CCX168 100 mg containing 400 μCi of [14C] on Day 1.	Drug: [14C]CCX168; Administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cumulative Percentage of the Administered Dose of [14C]CCX168 Recovered in Urine	Up to Day 15
Cumulative Percentage of the Administered Dose of [14C]CCX168 Recovered in Feces	Up to Day 15

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Experiencing Adverse Events (AEs)	Up to Day 29
Maximum Observed Concentration (Cmax) of Total Radioactivity in Plasma and Whole Blood	Up to Day 10
Time of Occurrence of Maximum Observed Concentration (Tmax) of Total Radioactivity in Plasma and Whole Blood	Up to Day 10
Elimination Rate Constant (λz) of Total Radioactivity in Plasma and Whole Blood	Up to Day 10
Apparent Terminal Half-life (t½z) of Total Radioactivity in Plasma and Whole Blood	Up to Day 10
Apparent Total Clearance (CL/F) of Total Radioactivity in Plasma and Whole Blood	Up to Day 10
Apparent Volume of Distribution (Vz/F) of Total Radioactivity in Plasma and Whole Blood	Up to Day 10
Area Under the Concentration-Time Curve from Time 0 to Time t (AUC0-t) of Total Radioactivity in Plasma and Whole Blood	Up to Day 10
Area Under the Concentration-Time Curve from Time 0 to Infinity (AUCinf) of Total Radioactivity in Plasma and Whole Blood	Up to Day 10
Area Under the Concentration-Time Curve from Time 0 to 24 Hours (AUC0-24) of Total Radioactivity in Plasma and Whole Blood	Up to 24 hours
Cmax of CCX168 and Metabolites in Plasma	Up to Day 10
Tmax of CCX168 and Metabolites in Plasma	Up to Day 10
λz of CCX168 and Metabolites in Plasma	Up to Day 10
t½z of CCX168 and Metabolites in Plasma	Up to Day 10
CL/F of CCX168 and Metabolites in Plasma	Up to Day 10
Vz/F of CCX168 and Metabolites in Plasma	Up to Day 10
AUC0-t of CCX168 and Metabolites in Plasma	Up to Day 10
AUCinf of CCX168 and Metabolites in Plasma	Up to Day 10
AUC0-24 of CCX168 and Metabolites in Plasma	Up to 24 hours
Percentage of Unchanged [14C]CCX168 Recovered in Urine, Feces, and Vomitus	Up to Day 15
Percentage of [14C]-Metabolite Recovered in Urine, Feces, and Vomitus	Up to Day 15
Amount of Unchanged [14C]CCX168 Recovered in Urine, Feces, and Vomitus (Auinf + Afinf + Avinf)	Up to Day 15
Amount of [14C]-Metabolite Recovered in Urine, Feces, and Vomitus (Amxuinf + Amxfinf + Amxvinf)	Up to Day 15
Renal Clearance (CLR) of [14C]CCX168	Up to Day 15
Renal Clearance of [14C]-Metabolite (CLRmx)	Up to Day 15
Number of Participants Experiencing Clinically Significant Changes in Laboratory Parameters	Up to Day 29
Number of Participants Experiencing Clinically Significant Changes in Vital Sign Parameters	Up to Day 29

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2014
• Primary Completion (Actual): December 5, 2014
• Study Completion (Actual): December 5, 2014

Study Registration Dates

• First Submitted: August 15, 2023
• First Submitted That Met QC Criteria: August 15, 2023
• First Posted (Actual): August 22, 2023

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 15, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Complement; Cardiovascular diseases; Vascular diseases; Systemic lupus erythematosus; Vasculitis; C5aR
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immune System Diseases; Autoimmune Diseases; Skin Diseases, Vascular; Systemic Vasculitis; Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
• Other Study ID Numbers: CL004_168

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No