Renal Impairment Clinical Trial
Official title:
A Phase I, Open-label and Single-dose Study to Evaluate the Pharmacokinetics and Safety of a Single 40 mg Oral Dose of ABL001 (Asciminib) in Subjects With Impaired Renal Function Compared to Matched Control Subjects With Normal Renal Function
Verified date | October 2021 |
Source | Novartis |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 14 |
Est. completion date | April 14, 2019 |
Est. primary completion date | March 18, 2019 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility | Inclusion Criteria: - 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) Exclusion Criteria: - 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 |
Country | Name | City | State |
---|---|---|---|
Bulgaria | Novartis Investigative Site | Sofia | |
Germany | Novartis Investigative Site | Berlin |
Lead Sponsor | Collaborator |
---|---|
Novartis Pharmaceuticals |
Bulgaria, Germany,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Pharmacokinetics: Plasma concentration of asciminib by AUClast | The AUC from time zero to the last measurable concentration sampling time (tlast) (ng*h/mL) | 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 | |
Primary | Pharmacokinetics: Plasma concentration of asciminib by AUCinf | The AUC from time zero to infinity (ng*h/mL) | 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 | |
Primary | Pharmacokinetics: Plasma concentration of asciminib by Cmax | The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (ng/mL) | 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 | |
Primary | Pharmacokinetics: Clearance of asciminib from plasma by CL/F | The total body clearance of drug from the plasma (L/h) | 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 | |
Secondary | Asciminib PK parameters unbound AUClast (AUClast)u and unbound AUCinf (AUCinf)u based on unbound fraction in plasma | 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) |
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 | |
Secondary | Asciminib PK parameters unbound Cmax (Cmax)u based on unbound fraction in plasma | The observed maximum unbound plasma concentration following administration (ng/mL) | 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 | |
Secondary | Asciminib secondary PK parameters Tmax, T1/2 | 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). |
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 | |
Secondary | Asciminib secondary PK parameter AUC0-72h | The area under the unbound plasma concentration-time curve from time zero to 72 h post-dosing (ng*h/mL) | 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 | |
Secondary | Asciminib secondary PK parameters Vz/F | apparent unbound drug volume of distribution during the terminal elimination phase following extravascular administration | 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 | |
Secondary | Percentage of participants with plasma protein binding as expressed by unbound fraction in plasma | asciminib plasma protein binding in subjects with impaired renal function and subjects with normal renal function | 2 hours post-dose |
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