None listed
Conditions
Brief summary
ACH-0144471 is an orally administered, small molecule, fD inhibitor that inhibits the alternative pathway of complement. Its alternative pathway inhibitory activity has been established in nonclinical studies, as well as in human healthy subjects in the single ascending dose study in healthy subjects (ACH471-001) that is ongoing in New Zealand. ACH-0144471 has the potential to treat multiple complement mediated diseases including paroxysmal nocturnal hemoglobinuria (PNH). In both the ACH471-001 (SAD) and ACH471-002 (MAD) clinical trials of ACH-0144471, an extemporaneously prepared LFC have been used. For continued development, more formulations of ACH-0144471 are being developed. The aim of this study is to determine the relative bioavailability and clinical safety of these two new formulations (tablet and softgel capsule) under fed and fasted conditions compared to the reference LFC formulation. The effect of food on the bioavailability of ACH-0144471 in the LFC will have been determined in the SAD study. The results from this study will provide quantitative information that will be used to determine doses of the new formulations that will provide similar exposures to those achieved by the LFC.
Interventions
Subjects will receive ACH-0144471 as Liquid Filled Capsule (LFC), tablet or Softgel capsules.
A total of 26 healthy subjects, between the ages of 18 and 55 years inclusive, will be enrolled into 2 groups. The first group, (Group 1), will have 18 subjects, and each will receive 3 single dose treatments.
The second group, (Group 2), will have 8 subjects, and each will receive 2 single dose treatments.
Subjects in Group 1 will be randomised to receive 1 of 3 treatments in an open label and 3-peri
Subjects will receive ACH-0144471 as Liquid Filled Capsule (LFC), tablet or Softgel capsules. A total of 26 healthy subjects, between the ages of 18 and 55 years inclusive, will be enrolled into 2 groups. The first group, (Group 1), will have 18 subjects, and each will receive 3 single dose treatments. The second group, (Group 2), will have 8 subjects, and each will receive 2 single dose treatments. Subjects in Group 1 will be randomised to receive 1 of 3 treatments in an open label and 3-period crossover study design. The three treatments are: A single dose of the LFC, fasted, followed by a 4-day (96 hour) washout. A single dose of the tablet, fed medium fat meal, followed by a 4-day (96 hour) washout. A single dose of the tablet, fasted, followed by a 4-day (96 hour) washout. Subjects in Group 2 will be randomised to receive 1 of 2 treatments in an open label and 2-period crossover study design. The two treatments are: A single dose of the LFC, fasted, followed by a 4-day (96 hour) washout. A single dose of the softgel capsule, fasted, followed by a 4-day (96 hour) washout. The ACH-0144471 dose to be used for all three formulations will be the same and will be determined based upon review of data from the ongoing single and multiple ascending dose studies. The ACH-0144471 daily dose will not exceed 1600 mg. The current ongoing studies are registered under the following ACTRN identifiers: Single Ascending Dose study ACH471-001 ACTRN 12616000082404 Multiple Ascending Dose study ACH471-002 ACTRN 12616000568415 All doses of ACH-0144471 will be administered orally and taken under direct observation of research staff. Dosing should be at the same time each day and the time of dose administration will be recorded.
Sponsors
Achillion Pharmaceuticals Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 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, 12-lead 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
If participants have any of the following criteria, they will be excluded from the study. - Smokers and have a clinically significant disease or allergy, - An active infection - Consume more than 21 alcoholic drinks/week. - Evidence of drug abuse or have taken prescription medications (systemic and topical) within 14 days prior to dosing.
Outcome results
None listed