A Study in Healthy Volunteers to Evaluate the Drug-Drug Interaction Potential of CCX168 With Concomitant Medications

• ClinicalTrials.gov Identifier: NCT06004947
• Recruitment Status: Completed
• First Posted: August 22, 2023
• Last Update Posted: August 22, 2023
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Study Description

Brief Summary:

The primary objective of this study will be to evaluate the drug-drug interaction potential of CCX168 with concomitant medications, as either a perpetrator or a victim, following oral administration of CCX168 to healthy participants.

Condition or disease	Intervention/treatment	Phase
Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis	Drug: CCX168; Drug: Midazolam; Drug: Celecoxib; Drug: Itraconazole; Drug: Rifampicin	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: An Open-Label, Phase 1 Study in Healthy Volunteers to Evaluate the Drug-Drug Interaction Potential of CCX168 With Concomitant Medications
• Actual Study Start Date: January 14, 2016
• Actual Primary Completion Date: March 15, 2016
• Actual Study Completion Date: June 10, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort A; A single dose of 2 mg midazolam (a Cytochrome P450 [CYP]3A4 probe drug) and a single dose of 200 mg celecoxib (a CYP2C9 probe drug) will be given orally concurrently on Day 1 and Day 13. On Day 3 through Day 18, CCX168 will be given orally at 30 mg twice daily (b.i.d.), and a single dose of 30 mg CCX168 will be given in the morning on Day 19. On Day 16 through Day 19, a once daily (q.d.) dose of 200 mg itraconazole (a CYP3A4 inhibitor) will be given orally.	Drug: CCX168; Administered orally.; Drug: Midazolam; Administered orally.; Drug: Celecoxib; Administered orally.; Drug: Itraconazole; Administered orally.
Experimental: Cohort B; A single dose of 30 mg CCX168 will be given on Day 1 and Day 14, while rifampicin (a CYP3A4 inducer) will be given at 600 mg once daily from Day 4 through Day 17.	Drug: CCX168; Administered orally.; Drug: Rifampicin; Administered orally.

Outcome Measures

Primary Outcome Measures :

1. Cohort A: Maximum Plasma Concentration (Cmax) of Midazolam [ Time Frame: Up to Day 13 ]
2. Cohort A: Cmax of Celecoxib [ Time Frame: Up to Day 13 ]
3. Cohort A: Time of Cmax (Tmax) of Midazolam [ Time Frame: Up to Day 13 ]
4. Cohort A: Tmax of Celecoxib [ Time Frame: Up to Day 13 ]
5. Cohort A: Area under the plasma concentration-time curve (AUC) from Time 0 to infinity of Midazolam [ Time Frame: Up to Day 13 ]
6. Cohort A: AUC from Time 0 to infinity of Celecoxib [ Time Frame: Up to Day 13 ]
7. Cohort A: Apparent Terminal Half Life of Midazolam [ Time Frame: Up to Day 13 ]
8. Cohort A: Apparent Terminal Half Life of Celecoxib [ Time Frame: Up to Day 13 ]
9. Cohort A: Cmax of CCX168 [ Time Frame: Day 15 up to Day 19 ]
10. Cohort A: Tmax of CCX168 [ Time Frame: Day 15 up to Day 19 ]
11. Cohort A: AUC Over the Dosing Interval of CCX168 [ Time Frame: Day 15 up to Day 19 ]
12. Cohort B: Cmax of CCX168 [ Time Frame: Up to Day 14 ]
13. Cohort B: Tmax of CCX168 [ Time Frame: Up to Day 14 ]
14. Cohort B: AUC from Time 0 to infinity of CCX168 [ Time Frame: Up to Day 14 ]
15. Cohort B: Apparent Terminal Half Life of CCX168 [ Time Frame: Up to Day 14 ]

Secondary Outcome Measures :

1. Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to Day 29 ]
2. Number of Participants Experiencing Clinically Significant Changes in Laboratory Parameters [ Time Frame: Up to Day 19 ]
3. Number of Participants Experiencing Clinically Significant Changes in Vital Sign Parameters [ Time Frame: Up to Day 19 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Male or female participants, aged 18-55 years inclusive, who are in generally good health as judged by the Investigator, whose body mass index is 19.0 to 32.0 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;
• Female participants of childbearing potential, or male participants with partners of childbearing potential may participate if adequate contraception is used during, and for at least 90 days after, any administration of study medication.

Exclusion Criteria:

• Pregnant or breastfeeding;
• Used a prescription and/or over-the-counter medication, with the exception of ibuprofen, hormonal contraceptives, and multi-vitamins, within 14 days prior to check-in; herbal supplements must be stopped 7 days prior to check-in;
• For at least 14 days prior to check-in and throughout the blood sample collection period, participants will not be allowed to eat any food or drink any beverage containing alcohol, grapefruit or grapefruit juice, apple or orange juice, vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard greens) and charbroiled meats; strenuous exercise must be stopped 4 days prior to check-in;
• History within the three months prior to check-in of use of tobacco and/or nicotine containing products;
• History within one year prior to check-in of illicit drug use;
• History of alcohol abuse at any time in the past;
• Has a history or presence of any form of cancer within the 5 years prior to check-in, with the exception of excised basal cell or squamous cell carcinoma of the skin, or cervical carcinoma in situ 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 unexplained syncope or family history of sudden death, or 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 11.5 g/dL for women or less than 13.0 g/dL for men, at screening or check-in, confirmed by a repeat measurement;
• Participated in any clinical study of an investigational product within 30 days prior to dosing or within 5 half-lives after dosing;
• Participant has any evidence of hepatic disease; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, or bilirubin greater than 1.5 times the upper limit of normal at screening or check-in;
• Participant's white blood cell count is below the lower limit of normal at screening or check-in, confirmed by a repeat measurement;
• Participant has any evidence of renal impairment; serum creatinine greater than 1.5 times the upper limit of normal at screening or check-in;
• Participant's urine tested positive at screening and/or check-in for any of the following: opioids, amphetamines and methamphetamines, cannabinoids, benzodiazepines, barbiturates, cocaine, cotinine, methylenedioxymethamphetamine (MDMA or "ecstasy"), methadone, phencyclidine, tri-cyclic antidepressants, or alcohol (Breathalyzer test allowed for alcohol).
• Participant is known as a CYP2C9 poor metabolizer.

Contacts and Locations

Locations

United States, Arizona

Celerion

Tempe, Arizona, United States, 85283

Sponsors and Collaborators

Amgen

Investigators

• Study Director: MD; Amgen

More Information

Additional Information:

AmgenTrials clinical trials website 

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT06004947
• Other Study ID Numbers: CL008_168
• First Posted: August 22, 2023
• Last Update Posted: August 22, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (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.
• URL: http://www.amgen.com/datasharing

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Amgen:

Renal diseases; Atypical hemolytic uremic syndrome; Immunoglobulin A nephropathy; Complement 5a receptor (C5aR); Complement

Additional relevant MeSH terms:

Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Vascular Diseases; Cardiovascular Diseases; Systemic Vasculitis; Skin Diseases, Vascular; Skin Diseases; Autoimmune Diseases; Immune System Diseases; Itraconazole; Rifampin; Celecoxib; Midazolam; Adjuvants, Anesthesia; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; GABA Modulators; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics