Pharmacokinetics Study of Asciminib in Subjects With Impaired Renal Function Compared to Matched Healthy Volunteers
- Registration Number
- NCT03605277
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
The purpose of this study is to characterize the pharmacokinetics (PK) and safety profile of asciminib following a single oral dose in adult subjects with renal impairment compared to a matched group of healthy subjects with normal renal function.
The results will determine whether or not a dose adjustment should be recommended when treating patients with asciminib who have impaired renal function.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 14
- Male or sterile / post-menopausal female
- BMI between 18 and 36 kg/m2, body weight greater than or equal to 50 kg and no more than 120 kg
- Adequate venous access for blood sampling
- For healthy volunteers: subject must be matched to at least one renal impaired subject by age (+/- 10 years), body weight (+/- 20%) and gender
- For renal impaired subjects: documented stable renal disease without evidence of progressive decline in renal function (stable renal disease is defined as no significant change, such as, stable aGFR < 90, for 12 weeks prior to study entry)
- women of child-bearing potential / pregnant / nursing
- contraindication or hypersensitivity to any drug or metabolites from similar class as asciminib or to any excipients of the study drug
- cardiac or cardiac repolarization abnormality
- history of psychiatric illness within the past 2 years
- history of acute or chronic pancreatitis
- subject on dialysis
- smokers (use of tobacco products in the previous 3 months) and not willing to abstain from using tobacco during the study
- any surgical or medical condition altering the absorption, distribution, metabolism or excretion of drug
- history of immunodeficiency diseases, including a positive Human Immunodeficiency Virus (HIV) test result at screening
- chronic infection with Hepatitis B virus (HBV) or Hepatitis C virus (HCV) at screening
- donation or loss of 400 mL or more of blood or plasma within 8 weeks prior to dosing or other amount considered to compromise the health of the subject if previous history of anemia exists
- use of the following drugs within 28 days prior to dosing: drugs that prolong the QT interval; CYP3A4 inhibitors and inducers; BCRP, UGT and PgP inhibitors and inducers
Other protocol-defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Severe renal impairment Asciminib subjects with severe renal impairment Normal renal function Asciminib healthy volunteers with normal renal function Moderate renal impairment Asciminib subject with moderate renal impairment Mild renal impairment Asciminib subjects with mild renal impairment
- Primary Outcome Measures
Name Time Method Pharmacokinetics: Plasma concentration of asciminib by AUClast pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose The AUC from time zero to the last measurable concentration sampling time (tlast) (ng\*h/mL)
Pharmacokinetics: Plasma concentration of asciminib by AUCinf pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose The AUC from time zero to infinity (ng\*h/mL)
Pharmacokinetics: Plasma concentration of asciminib by Cmax pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (ng/mL)
Pharmacokinetics: Clearance of asciminib from plasma by CL/F pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose The total body clearance of drug from the plasma (L/h)
- Secondary Outcome Measures
Name Time Method Asciminib PK parameters unbound AUClast (AUClast)u and unbound AUCinf (AUCinf)u based on unbound fraction in plasma pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose including but not limited to: (AUClast)u: area under the unbound plasma concentration-time curve calculated to the last quantifiable concentration point (ng\*h/mL)),
- (AUCinf)u: unbound plasma concentration-time curve extrapolated to infinity. It is calculated as AUCinf ,u= AUClast ,u+ Clast,u/Lambda_z. (ng\*h/mL)Asciminib PK parameters unbound Cmax (Cmax)u based on unbound fraction in plasma pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose The observed maximum unbound plasma concentration following administration (ng/mL)
Asciminib secondary PK parameters Tmax, T1/2 pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose including but not limited to:
* Tmax: the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (h)
* T1/2: the elimination half-life associated with the terminal slope (lz) of a semi logarithmic concentration-time curve (h).Asciminib secondary PK parameter AUC0-72h pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose The area under the unbound plasma concentration-time curve from time zero to 72 h post-dosing (ng\*h/mL)
Asciminib secondary PK parameters Vz/F pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose apparent unbound drug volume of distribution during the terminal elimination phase following extravascular administration
Percentage of participants with plasma protein binding as expressed by unbound fraction in plasma 2 hours post-dose asciminib plasma protein binding in subjects with impaired renal function and subjects with normal renal function
Trial Locations
- Locations (1)
Novartis Investigative Site
🇩🇪Berlin, Germany