None listed
Conditions
Brief summary
ACH0145228 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, 10 placebo) are planned for three treatment groups. Each healthy volunteer will receive a single dose of ACH0145228 or placebo. Subjects will remain inpatient from Day 1 to Day 4 with telephone calls on Day 5 and 6, and follow up visits (days 7, 14 and 28). The total duration of participation for each of these subjects will be approximately 28 days, not including screening.
Interventions
A total of 28 healthy volunteers (18 active, 10 placebo) are planned for three treatment groups and will receive a single oral dose of ACH-0145228 or placebo.
The first dose group (Group 1) will have 12 subjects randomized to 1:1 to active and placebo (6 active:6 placebo), the remaining dose groups will have 8 subjects per cohort randomized 3:1 to active and placebo (6 active and 2 placebo).
For each group, a sentinel group consisting of one active and one placebo subject will be dosed 24 hours
A total of 28 healthy volunteers (18 active, 10 placebo) are planned for three treatment groups and will receive a single oral dose of ACH-0145228 or placebo. The first dose group (Group 1) will have 12 subjects randomized to 1:1 to active and placebo (6 active:6 placebo), the remaining dose groups will have 8 subjects per cohort randomized 3:1 to active and placebo (6 active and 2 placebo). For each group, a sentinel group consisting of one active and one placebo subject will be dosed 24 hours before the remaining subjects. If no significant drug related toxicity is identified in the first 24 hours, then remaining subjects may be dosed. All dose escalation decisions will be made based on the review of data through Day 4 from the preceding dose. Safety will be evaluated by monitoring and assessing AEs, clinical laboratory tests, physical examination findings, vital signs measurements, and 12-lead ECG recordings at specified time points during the study. The starting minimum dose of ACH-0145228 will be 40mg and the maximum dose will be 160mg. The mode of administration will be Powder in Capsule (PIC) taken orally.
Sponsors
Achillion Pharmaceuticals, Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
25 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Be a healthy male or female of any ethnic origin between the ages of 25 and 55 years, inclusive. Healthy is defined as having no clinically relevant abnormalities identified by a detailed medical history, physical examination, blood pressure (BP) and heart rate measurements, 12-lead ECG, and clinical laboratory tests 2. Have a 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, as defined by 1 of the following: Surgical sterilization by hysterectomy, bilateral salpingo-oophorectomy or bilateral oophorectomy at least 6 months prior to dosing Postmenopausal with amenorrhea for at least 1 year prior to dosing and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status 4. Male subjects must agree to abstinence or use a condom when engaged in sexual activity, and agree to refrain from sperm donation, from check-in through at least 90 days after administration of study drug. Male subjects’ female partners of child-bearing potential must agree to use a highly effective form of contraception for the same time period 5. Be willing to answer inclusion and exclusion criteria questions 6. Give voluntary written informed consent to participate in the study 7. Be willing and able to comply with the visit schedule, treatment plan, laboratory tests, PK sampling schedule, and other study procedures
Exclusion criteria
1. Have a 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 PI 2. Have any condition possibly affecting drug absorption (including gastrectomy and cholecystectomy) 3. Test positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV) 4. Have C3 or C4 complement protein (C4) > 110% of the upper limit or < 90% of the lower limit of the reference ranges at screening 5. Have alternative pathway function (AH50) or classical pathway function (CH50) results outside the reference ranges at Screening 6. Have a body temperature greater than or equal to 38 degrees Celsius (°C) on Day -1 or Day 1, Hour 0 7. Have a history of febrile illness, or other evidence of infection, within 14 days prior to first study drug administration 8. Have a history of meningococcal infection, or a first-degree relative with a history of meningococcal infection 9. Have a history of seizures or any disorder of the brain 10. Have a history of hypersensitivity reactions to beta-lactams, penicillin, aminopenicillins, fluoroquinolones, cephalosporins, and carbapenems 11. Have a positive urine drug screen at Screening or Day -1. The urine drug screen should include, at a minimum, amphetamines, barbiturates, cotinine, cocaine metabolites, opiates, benzodiazepines, and cannabinoids 12. Be current tobacco users or 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 13. Have consumed any alcohol within 72 hours before first study drug administration or have a history of regular alcohol consumption exceeding 21 drinks/week (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months of screening 14. Have participated in a clinical study within 30 days prior to first study drug administration 15. Have a 12-lead ECG with clinically significant findings as judged by the PI or the PI’s designee at screening or prior to dosing on Day 1. Clinically significant findings should be based on the average of 3 recordings and include any of the following: QTcF > 450 msec PR interval > 220 msec QRS interval > 120 msec 16. Have clinically significant laboratory abnormalities, including any of the following, at either screening or Day -1: Serum creatinine > 1.5 × ULN or creatinine clearance < 80 mL/minute estimated by the Cockcroft-Gault formula [(140 - age) × weight (kg) / 72 × serum creatinine (mg/dL)] Alanine transaminase > ULN Aspartate transaminase > ULN Alkaline phosphatase > ULN Total bilirubin > 1.5 × ULN at screening Absolute neutrophil count (ANC) < lower limit of normal (LLN) Abnormal coagulation profile, including platelet count < LLN, partial thromboplastin time (PTT) > ULN, INR greater than the upper limit of the normal reference range (> 1.3) or prothrombin time (PT) > ULN Hemoglobin (Hb) < LLN Have a history or current evidence of biliary cholestasis 18. Have used prohibited medications as follows: Prescription medications (systemic and topical) within 14 days prior to first study drug administration (or when known, 5 half-lives, whichever is longer) through study completion, including follow-up visits Non prescription medications (including lipid-soluble vitamins A, D, E, and K [water-soluble vitamins B and C are not prohibited], herbal supplements, and dietary supplements) within 14 days of first study drug administration Medications known to induce or inhibit hepatic microsomal enzyme cytochrome P450 (CYP450) activity (e.g., quinines) within 28 days of first study drug administration Hormonal therapy/replacement medications within 28 days of first study drug administration 19. Consume an average of more than 8 cups of coffee or other caffeinated beverage, or 7 cans of cola per day 20. Have donated blood or lost more than 500 mL of blood within 3 months prior to first study drug administration 21. Have a clinically significant history of drug allergy as determined by the Investigator 22. Be unwilling or unable to comply with the study protocol for any reason 23. Have received a live attenuated vaccine within 30 days or other vaccine within 14 days of first study drug administration 24. Have received a blood transfusion or blood products within 6 months prior to first study drug administration 25. Have a diagnosis or history of Gilbert’s Syndrome, in the Investigator’s opinion
Outcome results
None listed