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 28 subjects (18 active and 10 placebo) are planned for three treatment groups. Additional subjects may be enrolled to replace discontinued subjects, or if more than three treatment groups are conducted (six active and two placebo subjects per group). Each healthy volunteer will receive a single dose of ACH-0144471 or placebo. Subjects will be housed from Day 1 to Day 4 and then return for follow-up visits on Days 7, 14, and 28. The total duration of participation for each of these subjects will be approximately 28 days, not including Screening.
Interventions
Subjects will receive either active (ACH-0144471) or placebo. At least three dose groups are planned. Group 1 will receive a single 200mg dose (consisting of two 100mg capsules), Group 2 will receive a single dose up to 600 mg and Group 3 will receive a dose up to 1500mg. ACH-0144471 may be given as divided doses over a 24-hour period. The maximum daily dose for this study will be calculated so that the predicted Cmax and ACH-0144471 AUC0-24 do not exceed the NOAEL observed in nonclinical s
Subjects will receive either active (ACH-0144471) or placebo. At least three dose groups are planned. Group 1 will receive a single 200mg dose (consisting of two 100mg capsules), Group 2 will receive a single dose up to 600 mg and Group 3 will receive a dose up to 1500mg. ACH-0144471 may be given as divided doses over a 24-hour period. The maximum daily dose for this study will be calculated so that the predicted Cmax and ACH-0144471 AUC0-24 do not exceed the NOAEL observed in nonclinical studies, and may be adjusted upward or downward based on emerging nonclinical and clinical safety, PK, and PD data. Treatment compliance will be observed by the research staff to ensure the subjects have taken his/her dose, and the time will be recorded in the source notes. In order to ensure adequate placebo subjects for comparison at the first dose, the first dose group (Group 1) will have will have 12 subjects, randomized 1:1 to active and placebo (six active and six placebo subjects); the remaining dose groups will have eight subjects per group randomized 3:1 to active and placebo (six active and two placebo subjects per group). In Group 1, a sentinel group consisting of one active and one placebo subject will be dosed before the other ten subjects in Group 1. If no significant drug-related toxicity is identified in the first 24 hours in the opinion of the PI, then remainder of Group 1 may be dosed. All dose escalation decisions will be made based on review of safety data through at least Day 4 from the preceding dose. However, after review of emerging data, the planned doses may be reduced, or a prior dose may be repeated. Higher than planned doses may also be considered, provided that previous doses were well-tolerated, and projected exposures at the higher than planned doses do not exceed the pre-specified exposure limits of the study, and do not exceed three times (3X) the corresponding exposures at the highest dose already studied. Based on emerging data from the first three dose groups, it will be determined if additional dose groups are warranted, and if so, at which doses and/or regimens (fed or fasted). These additional groups may be used to ensure adequate study of potential therapeutic doses, and/or to study the effect of food on the PK of ACH-0144471. A Dose Escalation Team (DET) consisting of, at a minimum, Principal Investigator, Medical Monitor, Clinical Pharmacologist, will review available safety, PK and PD data from preceding groups to decide whether the next group will proceed, and if so, at which dose level, and if at single administration or divided doses over 24 hours."
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
21 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy adult male or female subjects. Females must be of non-child bearing potential. Healthy is defined as having no clinically relevant abnormalities identified by a detailed medical history, physical exam, blood pressure and pulse rate measurements, 12lead ECG, and clinical laboratory tests. Healthy volunteers must have a normal weight defined as minimum body weight of 50 kg and a BMI of 18 to 30kg/m2.
Exclusion criteria
Healthy volunteers must not be smokers and not have a clinically significant disease or allergy, an active infection, or consume more than 21 alcoholic drinks/week. Volunteers must refrain from alcohol use for at least 72 hours prior to dosing (Day 1) and for the duration of the study. Volunteers must not have any evidence of drug abuse or taken prescription medications (systemic and topical) within 14 days prior to dosing.
Outcome results
None listed