None listed
Conditions
Brief summary
ACH-0145548 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 ACH-0145548 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 and 10 placebo) are planned for three treatment groups and will receive a single oral dose of ACH-0145548 or placebo.
The first dose group (Cohort 1) will have 12 subjects randomized to ratio of 1:1 to active and placebo (6 active: 6 placebo), the remaining dose groups (Cohort 2 and 3) will have 8 subjects per cohort randomized 3:1 to active and placebo (6 active and 2 placebo).
For each cohort, a sentinel group consisting of one active and one placebo
A total of 28 healthy volunteers (18 active and 10 placebo) are planned for three treatment groups and will receive a single oral dose of ACH-0145548 or placebo. The first dose group (Cohort 1) will have 12 subjects randomized to ratio of 1:1 to active and placebo (6 active: 6 placebo), the remaining dose groups (Cohort 2 and 3) will have 8 subjects per cohort randomized 3:1 to active and placebo (6 active and 2 placebo). For each cohort, 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 remainder of each cohort 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-0145548 will be 20 mg for Cohort 1, 60 mg for Cohort 2, and 120 or 180 mg for Cohort 3. The maximum dose will be 180 mg. All dose escalation decisions will be made based on the review of data through at least Day 4 from the preceding dose. The mode of administration will be Powder in Capsule (PIC) taken orally. Subjects will take their dose at the study site under direct observation by trained study personnel.
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. Participant must be 25 to 55 years of age, inclusive, at the time of signing the informed consent. 2. Participants who are overtly healthy as determined by medical evaluation including detailed medical history, physical examination, blood pressure (BP) and heart rate measurements, 12-lead ECG, and clinical laboratory tests. 3. Body weight of at least 50 kg and body mass index (BMI) within the range 18 to 30 kg/m2 (inclusive). 4. Male or Female Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Male participants Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days (a spermatogenesis cycle) after administration of study drug: Refrain from donating sperm PLUS either: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR Must agree to use a highly effective method of contraception with their partner(s) of childbearing potential. Their female partner(s) of childbearing potential must also agree to use a highly effective form of contraception for the same period. b. Female participants: Female participants must be of non-childbearing potential as defined by one of the following: Surgical sterilization by hysterectomy removal of uterus), bilateral salpingo-oophorectomy (removal of both ovaries and fallopian tubes) or bilateral oophorectomy (removal of both ovaries) at least 6 months prior to dosing Post-menopausal with amenorrhea (absence of menstrual periods) for at least 1 year prior to dosing and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status 5. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion criteria
1. Have a history or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders or conditions capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data. 2. Have a history of febrile illness, or other evidence of infection, within 14 days prior to first study drug administration 3. Have a history of meningococcal infection, or a first-degree relative with a history of meningococcal infection 4. Current or chronic history of liver disease or known hepatic or biliary abnormalities (including biliary cholestasis or Gilbert's syndrome) 5. Subjects with a female partner who is pregnant, nursing, or planning to become pregnant during the confinement phase of the study or within 90 days of study drug administration. 6. Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study 7. History of hypersensitivity reactions to beta-lactams, penicillin, aminopenicillins, fluoroquinolones, cephalosporins, and carbapenems 8. Use of prohibited over-the-counter or prescription 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 9. Live attenuated vaccine within 30 days or other vaccine within 14 days of first study drug administration 10. Donated blood or lost more than 500 ml of blood within 3 months prior to first study drug administration, or received a blood transfusion or blood products within 6 months prior to first study drug administration 11. Current enrolment or past participation within the last 30 days before study drug administration in any clinical study involving an investigational study intervention or any other type of medical research 12. Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to dosing 13. Positive hepatitis C antibody test result at screening or within 3 months prior to starting study intervention. 14. Positive human immunodeficiency virus (HIV) antibody test 15. Positive serum hCG (female participants only) 16. Have clinically significant laboratory abnormalities, including any of the following, at either screening or Day -1 : Serum creatinine greater than ULN and/or creatinine clearance less than 80 mL/minute estimated by the Cockcroft-Gault formula [(140 - age) × weight (kg) / 72 × serum creatinine (mg/dL)] Alanine transaminase greater than ULN Aspartate transaminase greater than ULN Alkaline phosphatase greater than ULN Total bilirubin greater than 1.5 × ULN Absolute neutrophil count (ANC) less than lower limit of normal (LLN) Absolute lymphocyte count (ALC) less than LLN Abnormal coagulation profile, including platelet count less than LLN, partial thromboplastin time (PTT) greater than ULN, INR greater than the upper limit of the normal reference range (greater than 1.3) or prothrombin time (PT) greater than ULN Hemoglobin (Hb) less than LLN 17. Clinically significant findings on a 12-lead ECG, as judged by the Principal Investigator (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 greater than or equal to 450 msec PR interval greater than 220 msec QRS interval greater than 120 msec 18. 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 19. Have C3 or C4 complement protein (C4) greater than 110% of the upper limit or less than 90% of the lower limit of the reference ranges at screening 20. Have alternative pathway function (AH50) or classical pathway function (CH50) results outside the reference ranges at screening 21. Have a body temperature greater than or equal to 38 degrees Celsius (°C) on Day -1 or Day 1, Hour 0 22. 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 23. 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 24. Consume an average of more than 8 cups of coffee or other caffeinated beverage, or 7 cans of cola per day
Outcome results
None listed