Renal ImpairmentPhase 1NCT03605277
Pharmacokinetics Study of Asciminib in Subjects With Impaired Renal Function Compared to Matched Healthy Volunteers
A Phase 1 study testing Asciminib in people with Renal Impairment, run by Novartis Pharmaceuticals at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Renal Impairment
- What is being tested?
- Asciminib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 16 Nov 2018to 14 Apr 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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
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.
- Conditions
- Renal Impairment
- Being tested
- Asciminib
- Keywords
- ABL001, asciminib, impaired renal function, pharmacokinetics
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AsciminibDrug
Also called ABL001
40 mg single dose
| Study group | Role | What they receive |
|---|---|---|
| Normal renal function | Experimental | healthy volunteers with normal renal function Receives: Drug: Asciminib |
| Severe renal impairment | Experimental | subjects with severe renal impairment Receives: Drug: Asciminib |
| Moderate renal impairment | Experimental | subject with moderate renal impairment Receives: Drug: Asciminib |
| Mild renal impairment | Experimental | subjects with mild renal impairment Receives: Drug: Asciminib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics: Plasma concentration of asciminib by AUClast
The AUC from time zero to the last measurable concentration sampling time (tlast) (ng*h/mL)
Measured: 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
Pharmacokinetics: Plasma concentration of asciminib by AUCinf
The AUC from time zero to infinity (ng*h/mL)
Measured: 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
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)
Measured: 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
Pharmacokinetics: Clearance of asciminib from plasma by CL/F
The total body clearance of drug from the plasma (L/h)
Measured: 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 outcomes (6)
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)
Measured: 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
Asciminib PK parameters unbound Cmax (Cmax)u based on unbound fraction in plasma
The observed maximum unbound plasma concentration following administration (ng/mL)
Measured: 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
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).
Measured: 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
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)
Measured: 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
Asciminib secondary PK parameters Vz/F
apparent unbound drug volume of distribution during the terminal elimination phase following extravascular administration
Measured: 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
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
Measured: 2 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2018
- Study start16 Nov 2018
- Primary completion18 Mar 2019
- Study completion14 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Renal ImpairmentStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03605277
- Sponsor's protocol ID
- CABL001A2105
- Other IDs
- 2018-001394-25, 2018
- Status last verified
- Oct 2021
- First submitted
- 20 Jul 2018
- Last updated
- 12 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hoch M, Sato M, Zack J, Quinlan M, Sengupta T, Allepuz A, Aimone P, Hourcade-Potelleret F. Pharmacokinetics of Asciminib in Individuals With Hepatic or Renal Impairment. J Clin Pharmacol. 2021 Nov;61(11):1454-1465. doi: 10.1002/jcph.1926. Epub 2021 Jul 16.
PubMed 34115385
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03605277
- Acronym / sponsor ID
- CABL001A2105
- Conditions
- Renal Impairment
- Keywords
- ABL001, asciminib, impaired renal function, pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 16 Nov 2018 (actual)
- Primary completion
- 18 Mar 2019 (actual)
- Study completion
- 14 Apr 2019 (actual)
- First posted
- 30 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Normal renal function | Experimental | Drug: Asciminibhealthy volunteers with normal renal function |
| Severe renal impairment | Experimental | Drug: Asciminibsubjects with severe renal impairment |
| Moderate renal impairment | Experimental | Drug: Asciminibsubject with moderate renal impairment |
| Mild renal impairment | Experimental | Drug: Asciminibsubjects with mild renal impairment |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AsciminibAlso: ABL00140 mg single dose | Drug | Mild renal impairment, Moderate renal impairment, Normal renal function, Severe renal impairment |
Primary outcome
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)
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)
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)
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)
6 secondary outcomes
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
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
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
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
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
Percentage of participants with plasma protein binding as expressed by unbound fraction in plasma
Time frame: 2 hours post-dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2021.
- Derived from this study: PubMed 34115385Hoch M, Sato M, Zack J, Quinlan M, Sengupta T, Allepuz A, Aimone P, Hourcade-Potelleret F. Pharmacokinetics of Asciminib in Individuals With Hepatic or Renal Impairment. J Clin Pharmacol. 2021 Nov;61(11):1454-1465. doi: 10.1002/jcph.1926. Epub 2021 Jul 16.
- Results for CABL001A2105 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
- A Plain Language Trial Summary is available on novartisclinicaltrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Asciminib in people with Renal Impairment, run by Novartis Pharmaceuticals at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Bulgaria, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03605277, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2021.