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A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CCX168 in Healthy Participants

Primary Purpose

Vasculitis, Systemic Lupus Erythematosus (SLE)

Status
Completed
Phase
Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
CCX168
Placebo
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Vasculitis focused on measuring Complement, C5aR, Vascular diseases, Cardiovascular diseases

Eligibility Criteria

19 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Male or female participants, aged 19-45 years inclusive, who are in generally good health, whose body mass index is 19 to 29 kg/m^2; 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 ECG), 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, and Female participants of childbearing potential, and male participants with partners of childbearing potential, may participate if adequate contraception is used during, and for at least the four weeks after, any administration of study medication. Exclusion Criteria: Women who are pregnant, breastfeeding, or have a positive serum pregnancy test at Screening and/or on Study Day -1; Expected requirement for use of any medication (with the exception of continuing 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) during the study period; 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; Consumed alcoholic beverages, or any food or drink containing grapefruit or grapefruit juice within 24 hours of screening; 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 randomization; Participant's hemoglobin less than 12 g/dL (or less than 7.45 mmol/L); Participated in any clinical study of an investigational product within 30 days prior to randomization; Participant has any evidence of hepatic disease; aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, or bilirubin > 1.5 x the upper limit of normal; Participant has any evidence of renal impairment; serum creatinine > 1.5 x upper limit of normal, and Participant's urine tested positive at Screening and/or on Study Day -1 for any of the following: opioids, amphetamines, cannabinoids, benzodiazepines, barbiturates, cocaine, cotinine, or alcohol (Breathalyzer test allowed for alcohol).

Sites / Locations

  • Covance Clinical Research Unit (CRU) AG

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Cohort 5

Arm Description

During Period 1, participants will receive a single dose of CCX168 1 mg or placebo. During the second study period, participants will receive the same dose as during the first period but once daily (QD) for a period of 7 days continuously.

During Period 1, participants will receive a single dose of CCX168 3 mg or placebo. During the second study period, participants will receive the same dose as during the first period but QD for a period of 7 days continuously.

During Period 1, participants will receive a single dose of CCX168 10 mg or placebo. During the second study period, participants will receive the same dose as during the first period but QD for a period of 7 days continuously.

During Period 1, participants will receive a single dose of CCX168 30 mg or placebo. During the second study period, participants will receive the same dose as during the first period or placebo twice daily (BID) for a period of 7 days continuously.

During Period 1, participants will receive a single dose of CCX168 100 mg or placebo. During the second study period, participants will receive the same dose as during the first period or placebo BID for a period of 7 days continuously.

Outcomes

Primary Outcome Measures

Number of Participants Experiencing Adverse Events (AEs)
Number of Participants Experiencing Clinically Significant Changes in Laboratory Parameters
Number of Participants Experiencing Clinically Significant Changes in Electrocardiogram (ECG) Parameters
Number of Participants Experiencing Clinically Significant Changes in Vital Sign Parameters

Secondary Outcome Measures

Maximum Plasma Concentration (Cmax) of CCX168
Time of Cmax of CCX168
Terminal Phase Rate Constant of CCX168
Apparent Terminal Half-life of CCX168
Apparent Oral Clearance of CCX168
Apparent Volume of Distribution of CCX168
Area Under the Plasma Concentration-time Curve (AUC) of CCX168 From Time 0 to Time t
AUC of CCX168 From Time 0 to Infinity
AUC of CCX168 From Time 0 to 24 Hours
AUC of CCX168 From Time 0 to 12 Hours
AUC of CCX168 From Time 12 to 24 Hours
Period 2: AUC of CCX168 From Time 0 to the end of the Dosing Interval
Period 2: Accumulation Ratio of CCX168
Percent Inhibition of complement 5a receptor (C5aR)-dependent Upregulation of CD11b in Peripheral Blood Neutrophils

Full Information

First Posted
August 2, 2023
Last Updated
August 2, 2023
Sponsor
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT05984251
Brief Title
A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CCX168 in Healthy Participants
Official Title
A Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CCX168 in Healthy Male and Female Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
December 21, 2009 (Actual)
Primary Completion Date
September 19, 2010 (Actual)
Study Completion Date
April 11, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary objective of this study will be to evaluate the safety and tolerability of single and multiple oral doses of CCX168, over a range of dose levels, in healthy male and female participants.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vasculitis, Systemic Lupus Erythematosus (SLE)
Keywords
Complement, C5aR, Vascular diseases, Cardiovascular diseases

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
During Period 1, participants will receive a single dose of CCX168 1 mg or placebo. During the second study period, participants will receive the same dose as during the first period but once daily (QD) for a period of 7 days continuously.
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
During Period 1, participants will receive a single dose of CCX168 3 mg or placebo. During the second study period, participants will receive the same dose as during the first period but QD for a period of 7 days continuously.
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
During Period 1, participants will receive a single dose of CCX168 10 mg or placebo. During the second study period, participants will receive the same dose as during the first period but QD for a period of 7 days continuously.
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
During Period 1, participants will receive a single dose of CCX168 30 mg or placebo. During the second study period, participants will receive the same dose as during the first period or placebo twice daily (BID) for a period of 7 days continuously.
Arm Title
Cohort 5
Arm Type
Experimental
Arm Description
During Period 1, participants will receive a single dose of CCX168 100 mg or placebo. During the second study period, participants will receive the same dose as during the first period or placebo BID for a period of 7 days continuously.
Intervention Type
Drug
Intervention Name(s)
CCX168
Intervention Description
Administered orally.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered orally.
Primary Outcome Measure Information:
Title
Number of Participants Experiencing Adverse Events (AEs)
Time Frame
Up to 43 days
Title
Number of Participants Experiencing Clinically Significant Changes in Laboratory Parameters
Time Frame
Up to 29 days
Title
Number of Participants Experiencing Clinically Significant Changes in Electrocardiogram (ECG) Parameters
Time Frame
Up to 29 days
Title
Number of Participants Experiencing Clinically Significant Changes in Vital Sign Parameters
Time Frame
Up to 29 days
Secondary Outcome Measure Information:
Title
Maximum Plasma Concentration (Cmax) of CCX168
Time Frame
Period 1: Up to Day 8; Period 2: Up to Day 15
Title
Time of Cmax of CCX168
Time Frame
Period 1: Up to Day 8; Period 2: Up to Day 15
Title
Terminal Phase Rate Constant of CCX168
Time Frame
Period 1: Up to Day 8; Period 2: Up to Day 15
Title
Apparent Terminal Half-life of CCX168
Time Frame
Period 1: Up to Day 8; Period 2: Up to Day 15
Title
Apparent Oral Clearance of CCX168
Time Frame
Period 1: Up to Day 8; Period 2: Up to Day 15
Title
Apparent Volume of Distribution of CCX168
Time Frame
Period 1: Up to Day 8; Period 2: Up to Day 15
Title
Area Under the Plasma Concentration-time Curve (AUC) of CCX168 From Time 0 to Time t
Time Frame
Period 1: Up to Day 8; Period 2: Up to Day 15
Title
AUC of CCX168 From Time 0 to Infinity
Time Frame
Period 1: Up to Day 8; Period 2: Up to Day 15
Title
AUC of CCX168 From Time 0 to 24 Hours
Time Frame
Periods 1 and 2: Up to Hour 24
Title
AUC of CCX168 From Time 0 to 12 Hours
Time Frame
Periods 1 and 2: Up to Hour 12
Title
AUC of CCX168 From Time 12 to 24 Hours
Time Frame
Periods 1 and 2: Hour 12 to Hour 24
Title
Period 2: AUC of CCX168 From Time 0 to the end of the Dosing Interval
Time Frame
Cohorts 1-3: Up to Hour 24; Cohorts 4-5: Up to Hour 12
Title
Period 2: Accumulation Ratio of CCX168
Time Frame
Up to Day 7
Title
Percent Inhibition of complement 5a receptor (C5aR)-dependent Upregulation of CD11b in Peripheral Blood Neutrophils
Time Frame
Period 1: Up to Hour 24; Period 2: Up to 12 hours after the first dose on Day 7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male or female participants, aged 19-45 years inclusive, who are in generally good health, whose body mass index is 19 to 29 kg/m^2; 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 ECG), 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, and Female participants of childbearing potential, and male participants with partners of childbearing potential, may participate if adequate contraception is used during, and for at least the four weeks after, any administration of study medication. Exclusion Criteria: Women who are pregnant, breastfeeding, or have a positive serum pregnancy test at Screening and/or on Study Day -1; Expected requirement for use of any medication (with the exception of continuing 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) during the study period; 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; Consumed alcoholic beverages, or any food or drink containing grapefruit or grapefruit juice within 24 hours of screening; 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 randomization; Participant's hemoglobin less than 12 g/dL (or less than 7.45 mmol/L); Participated in any clinical study of an investigational product within 30 days prior to randomization; Participant has any evidence of hepatic disease; aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, or bilirubin > 1.5 x the upper limit of normal; Participant has any evidence of renal impairment; serum creatinine > 1.5 x upper limit of normal, and Participant's urine tested positive at Screening and/or on Study Day -1 for any of the following: opioids, amphetamines, cannabinoids, benzodiazepines, barbiturates, cocaine, cotinine, or alcohol (Breathalyzer test allowed for alcohol).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Covance Clinical Research Unit (CRU) AG
City
Allschwil
ZIP/Postal Code
CH-4123
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
http://www.amgen.com/datasharing
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website

Learn more about this trial

A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CCX168 in Healthy Participants

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