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Pharmacokinetics Study of Asciminib in Subjects With Impaired Renal Function Compared to Matched Healthy Volunteers

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ClinicalTrials.gov Identifier: NCT03605277
Recruitment Status : Recruiting
First Posted : July 30, 2018
Last Update Posted : July 11, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( 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.


Condition or disease Intervention/treatment Phase
Renal Impairment Drug: Asciminib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Actual Study Start Date : November 16, 2018
Estimated Primary Completion Date : October 28, 2019
Estimated Study Completion Date : January 2, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Tests

Arm Intervention/treatment
Experimental: Normal renal function
healthy volunteers with normal renal function
Drug: Asciminib
40 mg single dose
Other Name: ABL001

Experimental: Severe renal impairment
subjects with severe renal impairment
Drug: Asciminib
40 mg single dose
Other Name: ABL001

Experimental: Moderate renal impairment
subject with moderate renal impairment
Drug: Asciminib
40 mg single dose
Other Name: ABL001

Experimental: Mild renal impairment
subjects with mild renal impairment
Drug: Asciminib
40 mg single dose
Other Name: ABL001




Primary Outcome Measures :
  1. Pharmacokinetics: Plasma concentration of asciminib by AUClast [ Time Frame: 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)

  2. Pharmacokinetics: Plasma concentration of asciminib by AUCinf [ Time Frame: 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)

  3. Pharmacokinetics: Plasma concentration of asciminib by Cmax [ Time Frame: 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)

  4. Pharmacokinetics: Clearance of asciminib from plasma by CL/F [ Time Frame: 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 :
  1. Asciminib PK parameters unbound AUClast (AUClast)u and unbound AUCinf (AUCinf)u based on unbound fraction in plasma [ Time Frame: 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)


  2. Asciminib PK parameters unbound Cmax (Cmax)u based on unbound fraction in plasma [ Time Frame: 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)

  3. Asciminib secondary PK parameters Tmax, T1/2 [ Time Frame: 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).

  4. Asciminib secondary PK parameter AUC0-72h [ Time Frame: 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)

  5. Asciminib secondary PK parameters Vz/F [ Time Frame: 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

  6. Percentage of participants with plasma protein binding as expressed by unbound fraction in plasma [ Time Frame: 2 hours post-dose ]
    asciminib plasma protein binding in subjects with impaired renal function and subjects with normal renal function



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03605277


Contacts
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Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals

Locations
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Bulgaria
Novartis Investigative Site Recruiting
Sofia, Bulgaria, 1612
Germany
Novartis Investigative Site Recruiting
Berlin, Germany, 14050
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03605277     History of Changes
Other Study ID Numbers: CABL001A2105
2018-001394-25 ( EudraCT Number )
First Posted: July 30, 2018    Key Record Dates
Last Update Posted: July 11, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
ABL001
asciminib
impaired renal function
pharmacokinetics
Additional relevant MeSH terms:
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Renal Insufficiency
Kidney Diseases
Urologic Diseases
Niacinamide
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs