None listed
Conditions
Brief summary
ACH-0144471 is a new orally (by mouth) administered complement factor D (fD) inhibitor being developed by Achillion Pharmaceuticals, Inc. for the treatment of complement mediated diseases. Many diseases are associated with inefficient control of complement or too much activity of the complement system. This study will help determine the correct dose, whether this medication has any side effects and how effective it is at controlling the complement system. A total of 46 subjects in four separate dose cohorts are planned. ACH-0144471 will be administered as multiple doses over a 14-day period. The dosing interval will be determined based on emerging data, and there will be flexibility to explore different dosing frequencies. In order to ensure sufficient placebo subjects for comparison at the first dose level, the first dose cohort will include 16 subjects, randomized 1:1 to active drug and placebo; the remaining dose cohorts will enroll 10 subjects per cohort, randomized 4:1 (8 active drug and 2 placebo).
Interventions
Subjects will receive either active (ACH-0144471) or placebo.
A total of 46 subjects in four separate dose cohorts are planned. ACH-0144471 will be administered as multiple doses over a 14-day period. The dosing interval will be determined based on emerging data, and there will be flexibility to explore different dosing frequencies. In order to ensure sufficient placebo subjects for comparison at the first dose level, the first dose cohort will include 16 subjects, randomized 1:1 to active drug
Subjects will receive either active (ACH-0144471) or placebo. A total of 46 subjects in four separate dose cohorts are planned. ACH-0144471 will be administered as multiple doses over a 14-day period. The dosing interval will be determined based on emerging data, and there will be flexibility to explore different dosing frequencies. In order to ensure sufficient placebo subjects for comparison at the first dose level, the first dose cohort will include 16 subjects, randomized 1:1 to active drug and placebo; the remaining dose cohorts will enroll 10 subjects per cohort, randomized 4:1 (8 active drug and 2 placebo). The dose for the first cohort will be determined based on the data from at least 2 doses in the currently ongoing SAD study (ACTRN12616000082404p) (clinical safety, observed PK/PD relationships). The dosing for the next cohort will proceed at a new dose level/regimen, based on the acceptability of available safety and PD results. This procedure will be repeated for all doses in this study. The maximum dose for this study will be calculated so that the predicted Cmax and AUC0-24 do not exceed the NOAELs observed in nonclinical studies, and may be adjusted upward or downward based on emerging nonclinical and clinical safety, PK, and PD data. All doses of ACH-0144471 or placebo will be administered orally. Dosing should be at the same time each day. All doses should be administered within 5 minutes of the scheduled time. All dosing is to occur during subject housing optimizing subject compliance.
Sponsors
Achillion Pharmaceuticals, Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
25 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male and female subjects of any ethnic origin between the ages of 25 and 55 years, inclusive 2. Body mass index (BMI) of 18 to 30 kg/m2 with a minimum body weight of 50 kg 3. Female subjects must be of non-childbearing potential 4. Male subjects must agree to abstinence or use a condom when engaged in sexual activity
Exclusion criteria
1. History or clinically relevant evidence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease in the opinion of the Principal Investigator (PI) 2. Any condition possibly affecting drug absorption (including gastrectomy or cholecystectomy) 3. Subjects with C3 complement protein (C3) or C4 complement protein (C4) >110% of the upper limit or <90% of the lower limit of the reference ranges at Screening 4. Subjects with alternative pathway hemolysis (AH50), or classical pathway hemolysis (CH50) assay results outside the reference ranges at Screening 5. Body temperature greater than or equal to 38 degrees C on Day – 1 or Day 1, Hour 0 6. History of febrile illness, or other evidence of infection, within 14 days prior to first study drug administration 7. History of meningococcal infection, or a first-degree relative with a history of meningococcal infection 8. Current tobacco users and smokers (defined as the use of any tobacco or nicotine-containing product within 3 months prior to first study drug administration) or a positive cotinine test at Screening or Day -1 9. History of hypersensitivity reactions to beta-lactams, penicillin, aminopenicillins, flouroquinolones (specifically including ciprofloxacin), cephalosporins, and carbapenems.
Outcome results
None listed