Complement alternative pathway disorders Other
Conditions
Interventions
This is a non-randomised, open-label study. Healthy volunteers will receive single oral doses of a new tablet formulation of the test medicine in up to six study periods and a single oral dose of the
Sponsors
Novartis (Switzerland)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1. Signed informed consent must be obtained prior to participation in the study. 2. Healthy male and non-childbearing potential female participants, 18 to 55 years of age, inclusive. 3. In good health as determined by past medical history, physical examination, ECG, and laboratory tests at screening and first baseline (admission). 4. Participants must weigh at least 50 kg at screening to participate in the study and must have a body mass index (BMI) within the range of 18.0 to 30.0 kg/m² at screening. 5. Normal or abnormal without clinical significance vital sign measurements at first baseline (admission) and first pre-dose. Supine vital signs should be within the following ranges: 5.1. Body temperature: =37.5°C 5.2. Pulse rate: 45-100 bpm 5.3. Systolic blood pressure: 90-140 mmHg 5.4. Diastolic blood pressure: 40-90 mmHg If the vital signs are out of range at first baseline and/or first pre-dose, two additional readings can be obtained so that up to three consecutive assessments are made, with the participant lying supine quietly for approximately 5 minutes preceding each repeat assessment. The last reading must be within the specified range for the participant to qualify. 6. Able to communicate well with the investigator to understand and comply with the requirements of the study.
Exclusion criteria
Exclusion criteria: 1. Participants who have received any IMP in a clinical research study within the 90 days or 5 half-lives, whichever is longer, prior to Period 1 Day 1. 2. Participants who are, or are immediate family members of, a study site or Sponsor employee. 3. History of hypersensitivity to the investigational compound/compound class or excipients being used in this study. 4. History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants participating in the study at screening or first baseline (admission) or first pre-dose such as: 4.1. Concomitant clinically significant cardiac arrhythmias, e.g., sustained ventricular tachycardia, and clinically significant second or third degree atrioventricular (AV) block without a pacemaker. 4.2. History of familial long QT syndrome or known family history of Torsades de Pointe. 4.3. QT interval corrected by Fridericia’s formula (QTcF) >450 milliseconds (ms) (males) or >460 ms (females) 5. History of symptomatic orthostatic hypotension or syncope. 6. A history of recurrent invasive infections caused by encapsulated organisms, e.g., meningococcus or pneumococcus. 7. Active systemic bacterial, viral (including SARS-CoV-2), parasitic or fungal infection within 14 days prior to study drug administration. 8. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years of screening, regardless of whether there is evidence of local recurrence or metastases. 9. Participants with a history of cholecystectomy or gall stones. 10. History or evidence of testicular disease (males). 11. Sexually active males unwilling to adhere to the contraception requirements of the study as detailed below: 11.1. A condom is required for all sexually active male participants to prevent them from fathering a child and to prevent delivery of the investigational drug via seminal fluid to their partner. 11.2. Males with partners of childbearing potential must use a condom during intercourse while taking investigational drug and for 95 days after stopping investigational drug (duration to cover one spermatogenesis cycle plus 5 half-lives) as a precautionary measure. 11.3. In addition to condoms, as a precaution, if a male has a female partner of childbearing potential, the partner must use a method of effective contraception from the list below whilst the male participant is taking the investigational drug for 95 days after he stops taking the investigational drug (duration to cover one spermatogenesis cycle plus 5 half-lives): 11.3.1. Partner’s bilateral tubal occlusion. 11.3.2. Partner’s use of oral (estrogen and progesterone; or progesterone only), injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example, a hormone vaginal ring or transdermal hormone contraception. 11.3.3. Male participant sterilization (vasectomy; at least 6 months prior to screening) is also appropriate. 11.3.4. Progesterone-only contraception where inhibition of ovulation is not the primary mechanism of action. 11.4. Female cap, diaphragm or sponge with spermicide. 11.5. Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Pharmacokinetic parameters of iptacopan (including but not limited to Cmax, AUClast, AUCinf, AUC0-24h, C24h and Tmax) measured using plasma drug concentration assay at pre-dose and at multiple post-dose timepoints until Period 7 Day 5 2. Relative bioavailability (Frel) for Cmax, C24h, AUClast, AUCinf and AUC0-24h (Tmax may be measured) of the iptacopan mmodified-release prototype tablets in comparison to the reference immediate-release capsule measured using plasma drug concentration assay at pre-dose and at multiple post-dose timepoints until Period 7 Day 5 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Safety endpoints measured using vital signs, electrocardiogram parameters, safety laboratory parameters and the incidence of adverse events at screening and at multiple post-dose timepoints until Period 7 Day 5 2. Relative bioavailability (Frel) for Cmax, C24h, AUClast, AUCinf and AUC0-24h (Tmax may be measured) of the iptacopan modified-release prototype tablet formulation(s) in the fed (test) versus fasted state (reference) measured using plasma drug concentration assay at pre-dose and at multiple post-dose timepoints until up to Period 7 Day 5 in applicable study periods | — |
Countries
England, United Kingdom
Contacts
Public ContactNovartis Study Director
Outcome results
None listed