A Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CCX872-B in Healthy Male and Female Subjects

CCX872-B is a new investigational compound that may eventually be used for the
treatment of diabetic nephropathy, a progressive kidney disease caused by
chronic diabetes. This is the first time that this compound is being given to
humans.

Primair:
To evaluate the safety and tolerability of single and multiple oral doses of
CCX872-B, over a range of dose levels, in healthy male and female subjects

Secundair:
To evaluate the following:
- Single and multiple dose pharmacokinetic profile of CCX872-B over a range of
dose levels
- Relationship between CCX872 plasma concentrations and CCR2 receptor blockade
on blood leukocytes, and
- Relationship between CCX872 plasma profile and changes in plasma MCP-1 and
circulating monocyte cell counts.

Screening and follow-up:
clinical laboratory, full physical examination, ECG, vital signs; at
eligibility screening: medical history, drug screen, HBsAg, anti HCV, anti-HIV
1/2 and pregnancy test (females only)

Observation period:
period 1: in clinic from -18h (Day -1) up to 24h (Day 2) after drug
administration (Day 1) with ambulatory visits on Day 3, 4 and 8
period 2: in clinic from -18h (Day -1) prior to first drug administration (Day
1) up to 24h (Day 8) after last drug administration (Day 7) with an ambulatory
visit on Day 15 and a follow-up phone call on Day 29.

Blood sampling:
For pharmacokinetics:
Period 1: Time 0 and at Hours 0.08 (5 minutes post dose), 0.25, 0.5, 1, 1.5, 2,
3, 4, 8, 12, and 16h after administration of study medication and once on Day
2, 3, 4 and 8
Period 2: Blood samples (4.0 mL) will be collected at Time 0 and at Hours 0.08
(5 minutes post dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, and 16 after
administration of the first dose of study medication if once daily is tested.
Blood samples (4.0 mL) collected at Time 0 and at Hours 0.25, 0.5, 1, 2, 3, 4,
8, 12, 12.25, 12.5, 13, 14, 15, and 16 after administration of the first dose
of study medication if twice daily is tested.
Blood samples (4.0 mL) will be collected at Hour 24 if a once daily dosing
regimen is tested, or Hours 20 and 24 if a twice daily dosing regimen is tested
(Day 2), Hour 48 (Day 3), Hour 72 (Day 4), Hour 96 (Day 5), and Hour 120 (Day
6) after administration of the first dose of study medication.
Blood samples (4.0 mL) will be collected at Hours 144, 144.08 (5 minutes post
dose), 144.25, 144.5, 145, 145.5, 146, 147, 148, 152, 156, and 160 (Day 7), and
Hour 168 (Day 8) after administration of the first dose of study medication if
once daily is tested. Blood samples (4.0 mL) will be collected at Hours 144,
144.25, 144.5, 145, 146, 147, 148, 152, 156, 156.25, 156.5, 157, 158, 159, and
160 (Day 7), and Hours 164 and 168 (Day 8) after administration of the first
dose of study medication if twice daily is tested.

For pharmacodynamics:
Period 1: 2h pre-dose 2 and 24 hours post-dose
Period 2: For CCR2 receptor occupancy and internalization assays, which will
only be conducted for the last 3 dose cohorts of Period 2: 1 x 10 mL plus 1 x 5
mL blood samples will be collected on Day 1, within 2 hours prior to the first
CCX872-B/placebo dose and at Hour 2, 2 hours after the first CCX872-B/placebo
dose, on Day 2 at Hour 24, prior to the morning dose of CCX872-B/placebo, on
Day 7 at Hour 146, 2 hours after the last CCX872-B/placebo dose, and on Day 8
at Hour 168, 12 or 24 hours after the last CCX872-B/placebo dose, depending on
whether twice daily or once daily dosing regimens are tested in Period 2. These
PD samples will be collected at the same time as the PK sample collections. For
peripheral blood monocyte subset counts: a blood sample (8 mL) will be
collected within 2 hours prior to the first dose of CCX872-B/placebo on Day 1
of Period 2, on Day 7 at Hour 146 (2 hours after the morning dose on Day 7),
and on Day 8, Hour 168 (12 or 24 hours after the last dose of CCX872-B/placebo,
depending on the dosing regimen).

Urine sampling:
For pharmacokinetics: Day 1 at interval 0-6h (Period 1 only)

Safety assessments:
Adverse events throughout the study. Clinical laboratory, hematology,
urinalysis, physical examination, vital signs, 12-lead-ECG and weight at
screening and follow-up

Period 1: subjects will receive a single dose of CCX872-B as a capsule
Period 2: subjects will receive multiple doses of CCX872-B as a capsule once or
twice daily for a total of 7 days

Registration af adverse effects: During the entire investigation all adverse
effect you report will be documented.
Blood draw, indwelling canula: During this study not more than 600 ml of blood
will be drawn. It is anticipated that in period 1 once (Day 1) an indwelling
cannula will be used and in period 2 twice (Day 1 and Day 7). The remainder of
the blood draws will be drawn by direct puncture of the vein.
Collection of urine: In period 1, urine will be collected starting after dosing
until 6 hours after administration of CCX872-B.
Heart trace (ECG*s): ECG*s will be made regularly: specifically on Day 1 of
period 1 and on Day 1 and 7 of period 2.