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Liver DiseasesPhase 1NCT04639115

A Phase 1, Multicenter, Open-Label Study to Evaluate the Effect of Mild or Moderate Hepatic Impairment on the Multiple-Dose Pharmacokinetics of Ozanimod

A Phase 1 study testing Ozanimod in people with Liver Diseases and Digestive System Diseases, run by Celgene at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a Phase 1, multicenter, nonrandomized, open-label, parallel-group study in participants with mild or moderate hepatic impairment, and in participants with normal hepatic function. Read more about this study

Who is it for?
Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for
Liver Diseases, Digestive System Diseases
What is being tested?
Ozanimod
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
3 sitesUnited States
Study dates
18 Dec 2020to 6 Apr 2022
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 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Acceptable methods of birth control in this study are the following:
  • Combined hormonal (oestrogen and progestogen containing) contraception, which may be oral, intravaginal, or transdermal
  • Progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable
  • Placement of an intrauterine device or intrauterine hormone-releasing system
  • Bilateral tubal occlusion
  • Vasectomized partner
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  • Complete sexual abstinence
  • All participants:
  • Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception.
  • Inclusion Criteria for Participants with Mild or Moderate Hepatic Impairment (Groups 1 and 2)
  • Each participant with mild or moderate hepatic impairment must satisfy the following criteria to be enrolled in the study:
  • Participant has mild (5 to 6 points) or moderate (7 to 9 points) hepatic impairment per the Child-Pugh system (Appendix B).
  • Participant should be enrolled into the group corresponding to the Child-Pugh classification score that most accurately reflects the most severe hepatic disease classification within the past 6 months of signing the ICF (based on past medical history or PE observation).
  • If a Child-Pugh score was previously calculated and documented in the last 6 months, and it is more severe than the one calculated at Screening, then that previous value will be used for study entry purposes. If the Screening Child-Pugh score is more severe, then it will be used. If no score was calculated in the 6 months prior to Screening, then the score obtained at Screening will be used. Adequate documentation should be provided to substantiate the Child-Pugh score assigned to each participant.
  • Participant must be medically stable for at least 4 weeks before Screening with clinically acceptable medical history (eg, no worsening of clinical signs of hepatic impairment, or no worsening of total bilirubin or prothrombin time by more than 50%), PE, clinical laboratory tests, vital signs, and 12-lead ECGs consistent with the underlying stable hepatic impairment condition, as judged by the Investigator.
  • Participant with laboratory parameters that are considered clinically significant beyond those consistent with their degree of hepatic impairment may be included if, in the opinion of the Investigator and Medical Monitor, these findings will not interfere with the study or introduce additional safety risk to the participant.
  • Participant must be stable on a concomitant medication and/or treatment regimen (defined as not starting a new treatment/medication[s] or a change in the dosage or frequency of the concomitant medication[s] within 2 weeks before dosing with ozanimod).
  • Participant must have estimated creatinine clearance ≥ 50 mL/min at Screening as calculated by the Cockcroft-Gault formula.
  • Inclusion Criteria for Matched Normal Hepatic Function Participants (Group 3)
  • Each matched participant must satisfy the following criteria to be enrolled in the study:
  • Participant is in good health as determined by past medical history, PE, vital signs, ECG, and clinical laboratory safety tests. Clinical laboratory safety tests (ie, hematology, coagulation, chemistry, and urinalysis) must be within normal limits or clinically acceptable as judged by the Investigator.
  • Participant must match a participant in Groups 1 and/or 2, with respect to sex, age (± 10 years), weight (± 20%) and smoking status. One normal hepatic function participant can be matched to 2 hepatic impairment participants (one in Group 1 and one in Group 2), but no more than one hepatic impairment participant in the same group.

Who cannot join

  • The presence of any of the following will exclude a participant from enrollment:
  • Participant has any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study.
  • Participant has any condition that confounds the ability to interpret data from the study.
  • Participant has a seated blood pressure outside 90 to 155 mmHg systolic or 50 to 95 mmHg diastolic at Screening or Day -1.
  • Participant has a seated pulse rate outside 55 to 90 beats per minute (bpm) at Screening or Day -1.
  • Participant has a positive serum test for human immunodeficiency virus (HIV) at Screening or Day -1.
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  • Participant with any active infection including hepatitis.
  • Participant has a positive alcohol urine or breath test at Screening or Day -1.
  • Participant has received any investigational drug within 30 days or 5 times the elimination half-life (if known), whichever is longer, prior to the first dose of IP.
  • Participant has consumed pomelo-variety citrus fruits or juice (including pomelo, grapefruit, Seville oranges) within 7 days prior to the first dose of IP or herbal supplements including St. John's wort within 28 days prior to the first dose of IP.
  • Participant fails or is unwilling to abstain from strenuous physical activities for at least 24 hours prior to the first dose of IP.
  • Participant has poor peripheral venous access.
  • Participant has donated greater than 400 mL of blood within 60 days prior to Day 1.
  • Participant has history of hypersensitivity or allergic reaction to S1P receptor modulators.
  • Participant has used any of the following systemic medications:
  • Strong inhibitors of CYP3A, and all inhibitors of CYP2C8 or BCRP, (ie, cyclosporine, eltrombopag, gefitinib) within 7 days or 5 half-lives, whichever is longer, prior to Day 1, or
  • Strong inducers of CYP3A, and all inducers of CYP2C8 within 14 days or 5 halflives, whichever is longer, prior to Day 1, or
  • Any known MAO inhibitors within 30 days or 5 half-lives, whichever is longer, prior to Day 1. Examples of MAO inhibitors include but are not limited to phenelzine, selegiline, isocarboxazid, rasagiline, tranylcypromine, pargyline, procarbazine, and furazolidone.
  • Participant who in the last 6 months of signing the ICF experienced myocardial infarction, unstable angina, stroke, transient ischaemic attack, decompensated heart failure requiringmhospitalization or New York Heart Association (NYHA) Class III/IV heart failure.
  • Participant with history or presence of second-degree atrioventricular (AV) block Type II or third-degree AV block or sick sinus syndrome unless the patient has a functioning pacemaker.
  • Participant with history of cardiac arrest, cerebrovascular disease, uncontrolled hypertension, or severe untreated sleep apnoea, history of recurrent syncope or symptomatic bradycardia
  • Participant with pre-existing significant QT interval prolongation (QTc greater than 500 msec) or other risks for QT prolongation, and patients on medicinal products other than beta-blockers and calcium-channel blockers that may potentiate bradycardia.
  • Participant on class Ia (eg, quinidine, disopyramide) or class III (eg, amiodarone, sotalol) antiarrhythmic medicinal products, which have been associated with cases of torsades de pointes in patients with bradycardia have not been studied with ozanimod.
  • Exclusion Criteria for Participants with Hepatic Impairment (Groups 1 and 2)
  • The presence of any of the following will exclude a hepatically-impaired participant from enrollment:
  • Participant has any serious medical condition (excluding hepatic impairment and related complications), clinically significant laboratory abnormality not related to hepatic impairment and related complications, or psychiatric illness that would prevent the participant from participating in the study per Investigator discretion.
  • Participant has current hepatic encephalopathy with time-or place-disorientation, somnolence, stupor, coma, no personality/behavior, rigidity, or hyperactive reflexes - or has had such within 1 month of Screening.
  • Participant has planned liver transplantation within 6 months of Screening or has received a liver transplant, transjugular intrahepatic portosystemic shunt, or transjugular intrahepatic portosystemic stent shunting procedure.
  • Participant has a history of alcoholism, drug abuse, or addiction within 6 months prior to Screening.
  • Participant has a positive urine drug screen including cotinine (non-smokers and former smokers only) (except for prescribed medications such as benzodiazepines) at Screening or Day -1. Tetrahydrocannabinol use (as permitted by local law) is not allowed within 14 days prior to Day 1 and during the study.
  • Participant has any history of cholecystectomy, clinically significant cardiovascular or cerebrovascular disease.
  • Participant has severe ascites at Screening or Day -1.
  • Participant has hepatocellular carcinoma or acute liver disease (eg, caused by an infection or drug toxicity).
  • Participant chronically or routinely uses more than 2 g of acetaminophen daily.
  • Exclusion Criteria for Matched Normal Hepatic Function Participants (Group 3)
  • The presence of any of the following will exclude a matched normal hepatic function participant from enrollment:
  • Participant has any significant medical condition or psychiatric illness that would prevent the participant from participating in the study (as determined by the Investigator).
  • Participant has a history of alcoholism, drug abuse, or addition within 24 months prior to Screening.
  • Participant has a positive test result for hepatitis B surface antigen and/or hepatitis C antibody.
  • Participant has a positive urine drug test (except for cotinine in smokers) at Screening or Day -1.
  • Participant has used any systemic over-the-counter medication (excluding acetaminophen up to 2 g/day and low dose aspirin) within 7 days prior to Day 1, or any systemic prescription medication (except for contraceptives) within 28 days or 5-half-lives, whichever is longer, prior to Day 1.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Miami Miller School of Medicine

    Miami, Florida, 33136

  • Orlando Clinical Research Center OCRC

    Orlando, Florida, 32809

  • The Texas Liver Institute

    San Antonio, Texas, 78215

Other trials in United States

About this study

This is a Phase 1, multicenter, nonrandomized, open-label, parallel-group study in participants with mild or moderate hepatic impairment, and in participants with normal hepatic function.

Degrees of hepatic impairment will be determined during screening by the participant's score according to Pugh's Modification of Child's Classification of Severity of Liver Disease.

Read more

Participants will be enrolled in Groups 1 through 3 as follows:

  • Group 1 (mild hepatic impairment): A total of approximately 8 participants with a Child-Pugh score of 5 to 6.
  • Group 2 (moderate hepatic impairment): A total of approximately 8 participants with a Child-Pugh score of 7 to 9.
  • Group 3 (normal hepatic function): Approximately 8 to 16 participants will be matched to Participants in Groups 1 and 2. Normal hepatic function participants are allowed to match multiple hepatic impairment participants. Participants will be matched by sex, age (± 10 years), weight (± 20%), and smoking status.
Being tested
Ozanimod
Keywords
Mild and moderate Hepatic impairment, Healthy volunteer, Ozanimod
Medical subject headings
Liver Diseases, Digestive System Diseases, Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OzanimodDrug

    Also called RPC-1063, Zeposia

    Ozanimod

Study groups in NCT04639115
Study groupRoleWhat they receive
Ozanimod in subjects with mild hepatic impairmentExperimentalParticipants will receive ozanimod 0.23 mg once daily (QD) on Days 1 to 4, 0.46 mg QD on Days 5 to 7, and 0.92 mg QD on Day 8 in subjects with mild hepatic impairment
Receives: Drug: Ozanimod
Ozanimod in subjects with moderate hepatic impairmentExperimentalParticipants will receive ozanimod 0.23 mg once daily (QD) on Days 1 to 4, 0.46 mg QD on Days 5 to 7, and 0.92 mg QD on Day 8 in subjects with moderate hepatic impairment
Receives: Drug: Ozanimod
Ozanimod in healthy subjectsExperimentalParticipants will receive ozanimod 0.23 mg once daily (QD) on Days 1 to 4, 0.46 mg QD on Days 5 to 7, and 0.92 mg QD on Day 8 in healthy subjects
Receives: Drug: Ozanimod

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pharmacokinetics - AUClast on Day 8 (Ozanimod, CC112273 and CC1084037)

    AUC from time zero to the last measured time point

    Measured: Up to day 8

  2. Pharmacokinetics - AUC∞ on Day 8 (Ozanimod, CC112273 and CC1084037)

    Area under the plasma concentration-time curve from time zero extrapolated to infinity

    Measured: Up to day 8

  3. Pharmacokinetics - Cmax on Day 8 (Ozanimod, CC112273 and CC1084037)

    Maximum observed plasma concentration

    Measured: Up to day 8

  4. Pharmacokinetics - Cmin on Day 8 (Ozanimod, CC112273 and CC1084037)

    Minimum observed plasma concentration

    Measured: Up to day 8

  5. Pharmacokinetics - AUCtau on Day 8 (Ozanimod, CC112273 and CC1084037)

    Area under the plasma concentration-time curve from time zero to dosing interval

    Measured: Up to day 8

Secondary outcomes (15)

  1. Adverse Events (AEs)

    An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a Participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the Participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE

    Measured: From the time the ICF is signed until 64 ± 3 days after the last dose of ozanimod treatment

  2. Pharmacokinetics -Cmax on Days 1 and 5 (Ozanimod, CC112273 and CC1084037)

    Maximum observed plasma concentration

    Measured: Days 1 and 5

  3. Pharmacokinetics -Cmin on Days 1 and 5 (Ozanimod, CC112273 and CC1084037)

    Minimum observed plasma concentration

    Measured: Days 1, and 5

  4. Pharmacokinetics - AUCtau on Days 1 and 5 (Ozanimod, CC112273 and CC1084037)

    Area under the plasma concentration-time curve from time zero to dosing interval

    Measured: Days 1 and 5

  5. Pharmacokinetics - Tmax (Ozanimod, CC112273 and CC1084037)

    Time to reach maximum observed plasma concentration

    Measured: Days 1, 5, and 8

  6. Pharmacokinetics - AUClast (Ozanimod, CC112273 and CC1084037)

    AUC from time zero to the last measured time point

    Measured: From Day 8 till Day 72

  7. Pharmacokinetics - t1/2 (Ozanimod, CC112273 and CC1084037)

    Terminal elimination half-life

    Measured: From Day 8 till Day 72

  8. Pharmacokinetics - Vz/F (Ozanimod)

    Apparent volume of distribution when dosed orally

    Measured: From Day 8 till Day 72

  9. Pharmacokinetics - CL/F (Ozanimod)

    Apparent total plasma clearance when dosed orally

    Measured: From Day 8 till Day 72

  10. Pharmacokinetics - fu (Ozanimod, CC112273 and CC1084037)

    Unbound fraction

    Measured: Day 1 and Day 8

  11. Pharmacokinetics - Cmax,u (Ozanimod, CC112273 and CC1084037)

    Maximum observed plasma concentration

    Measured: Days 1, 5, and 8

  12. Pharmacokinetics - AUC∞,u (Ozanimod, CC112273 and CC1084037)

    Unbound AUC∞

    Measured: From Day 8 till Day 72

  13. Pharmacokinetics - AUClast,u (Ozanimod, CC112273 and CC1084037)

    Unbound AUClast

    Measured: From Day 8 till Day 72

  14. Pharmacokinetics - AUCtau,u (Ozanimod, CC112273 and CC1084037)

    Unbound AUCtau

    Measured: Days 1, 5, and 8

  15. Pharmacokinetics - M/P AUCtau ratio (CC112273 and CC1084037)

    Molecular weight corrected metabolite-to-parent AUC from time zero to dosing interval ratio

    Measured: Days 1, 5, and 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Nov 2020
  2. Study start18 Dec 2020
  3. Primary completion6 Apr 2022
  4. Study completion6 Apr 2022

Resources

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
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04639115
Sponsor's protocol ID
RPC-1063-CP-004
Other IDs
U1111-1257-6851
Status last verified
Jun 2022
First submitted
17 Nov 2020
Last updated
14 Jun 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ozanimod in people with Liver Diseases and Digestive System Diseases, run by Celgene at 3 sites in United States.

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 22 inclusion and 41 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 14 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. 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 - AUClast on Day 8 (Ozanimod, CC112273 and CC1084037) (time frame: Up to day 8). The study lists 5 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 NCT04639115.

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 14 Jun 2022.

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