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

Sponsor

Amgen (Industry)

Overall Status

Completed

CT.gov ID

NCT05984251

Collaborator

(none)

Enrollment

Location

Arms

15.6

Actual Duration (Months)

3.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Vasculitis Systemic Lupus Erythematosus (SLE)	Drug: CCX168 Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

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

Actual Study Start Date :

Dec 21, 2009

Actual Primary Completion Date :

Sep 19, 2010

Actual Study Completion Date :

Apr 11, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 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.	Drug: CCX168 Administered orally. Drug: Placebo Administered orally.
Experimental: Cohort 2 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.	Drug: CCX168 Administered orally. Drug: Placebo Administered orally.
Experimental: Cohort 3 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.	Drug: CCX168 Administered orally. Drug: Placebo Administered orally.
Experimental: Cohort 4 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.	Drug: CCX168 Administered orally. Drug: Placebo Administered orally.
Experimental: Cohort 5 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.	Drug: CCX168 Administered orally. Drug: Placebo Administered orally.

Outcome Measures

Primary Outcome Measures

Number of Participants Experiencing Adverse Events (AEs) [Up to 43 days]
Number of Participants Experiencing Clinically Significant Changes in Laboratory Parameters [Up to 29 days]
Number of Participants Experiencing Clinically Significant Changes in Electrocardiogram (ECG) Parameters [Up to 29 days]
Number of Participants Experiencing Clinically Significant Changes in Vital Sign Parameters [Up to 29 days]

Secondary Outcome Measures

Maximum Plasma Concentration (Cmax) of CCX168 [Period 1: Up to Day 8; Period 2: Up to Day 15]
Time of Cmax of CCX168 [Period 1: Up to Day 8; Period 2: Up to Day 15]
Terminal Phase Rate Constant of CCX168 [Period 1: Up to Day 8; Period 2: Up to Day 15]
Apparent Terminal Half-life of CCX168 [Period 1: Up to Day 8; Period 2: Up to Day 15]
Apparent Oral Clearance of CCX168 [Period 1: Up to Day 8; Period 2: Up to Day 15]
Apparent Volume of Distribution of CCX168 [Period 1: Up to Day 8; Period 2: Up to Day 15]
Area Under the Plasma Concentration-time Curve (AUC) of CCX168 From Time 0 to Time t [Period 1: Up to Day 8; Period 2: Up to Day 15]
AUC of CCX168 From Time 0 to Infinity [Period 1: Up to Day 8; Period 2: Up to Day 15]
AUC of CCX168 From Time 0 to 24 Hours [Periods 1 and 2: Up to Hour 24]
AUC of CCX168 From Time 0 to 12 Hours [Periods 1 and 2: Up to Hour 12]
AUC of CCX168 From Time 12 to 24 Hours [Periods 1 and 2: Hour 12 to Hour 24]
Period 2: AUC of CCX168 From Time 0 to the end of the Dosing Interval [Cohorts 1-3: Up to Hour 24; Cohorts 4-5: Up to Hour 12]
Period 2: Accumulation Ratio of CCX168 [Up to Day 7]
Percent Inhibition of complement 5a receptor (C5aR)-dependent Upregulation of CD11b in Peripheral Blood Neutrophils [Period 1: Up to Hour 24; Period 2: Up to 12 hours after the first dose on Day 7]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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).