Healthy VolunteerPhase 1NCT04268394
A Study to Evaluate Potential Cytochrome P450 and Transporter Protein Interactions With CC-99677
A Phase 1 study testing CC-99677, Methotrexate and Sulfasalazine in people with Healthy Volunteer, run by Celgene at 1 site in United Kingdom.
Trial summary
It is a phase 1, open-label, single-center, three-part study to assess the safety, tolerability, and pharmacokinetics of multiple doses of CC-99677 administered alone or in combination with either methotrexate and sulfasalazine; itraconazole, rifampin, midazolam, or a cocktail of digoxin, metformin, and rosuvastatin… Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteer
- What is being tested?
- CC-99677, Methotrexate and Sulfasalazine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 13 Mar 2020to 2 Jun 2021
- 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 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects must satisfy all of the following criteria to be enrolled in the study:
- Subject is ≥ 18 and ≤ 64 years of age at the time of signing the informed consent form (ICF).
- Part 1 is open to male subjects ONLY
- Both male and female subjects may participate in Parts 2-3.
- Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
- Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
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- Subject is in good health, as determined by the Investigator based on a physical examination at screening.
- Female subjects of childbearing potential (FCBP) are not permitted in Part 1, but are permitted in Parts 2 and 3, and must:
- Have two (2) negative pregnancy tests as verified by the Investigator prior to the first dose of IP. She must agree to ongoing pregnancy testing during the course of the study, and prior to discharge from the study site. This applies even if the subject practices true abstinence2 from heterosexual contact.
- Agree to use, and be able to comply with, one highly effective3 non-hormonal method of contraception without interruption, during the study (including any dose interruptions), and for at least 28 days after discontinuation of IP. The female subject's chosen form of highly effective contraception must be effective by the time the female subject is enrolled into the study (eg, contraception should be initiated at least 28 days prior to enrollment) and at least 28 days after discontinuation of IP.
- Female subjects NOT of childbearing potential are permitted in all Parts except Part 1, and must:
- Have been surgically sterilized (hysterectomy or bilateral oophorectomy; proper documentation is required) at least 6 months before screening, or be postmenopausal (defined as 24 consecutive months without menses before screening, with a follicle stimulating hormone [FSH] level of > 40 IU/L at screening).
- Male subjects must:
- For Part 1: Agree to use a latex or other synthetic condom during sexual contact with a pregnant female or a FCBP while participating in the study, during any dose interruptions, and for at least -6 months after discontinuation of methotrexate (Methotrexate Summary of Product Characteristics [SmPC]; CTFG, 2014). In addition, any non-pregnant FCBP partner of a male subject must use a reliable contraception method, without interruption, during the study (including any dose interruptions) and for at least 6 months after discontinuation of methotrexate (Methotrexate SmPC). It is recommended that non-pregnant FCBP partners of male subjects in Part 1 use approved highly effective contraception as a reliable method. Examples of approved methods of highly effective contraception include combined hormonal contraception; progestogen only oral hormonal contraception; intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; vasectomized male partner (CTFG, 2014).
- For Parts 2 and 3: Agree to use a latex or other synthetic condom during sexual contact with a pregnant female or a FCBP while participating in the study, during any dose interruptions, and for at least 28 days after discontinuation of IP, even if he has undergone a successful vasectomy. In addition, any non-pregnant FCBP partner of a male subject must use an approved method of effective contraception, without interruption, during the study (including any dose interruptions) and for at least 28 days after discontinuation of IP (CTFG, 2014). Examples of approved methods of effective contraception for non-pregnant FCBP partners include progestogen only oral hormonal contraception; male or female condom with or without spermicide; or cap, diaphragm, or sponge with spermicide.
- Subject has a body mass index (BMI) ≥ 18 and ≤ 30 kg/m2 at screening.
- Subject has clinical laboratory safety test results that are within normal limits or considered not clinically significant by the Investigator. In addition, ALT, AST, and total bilirubin must be ≤ the upper limit of normal at screening and on Day -1. Platelet count, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) must be ≥ the lower limit of normal at screening and on Day -1.
- Subject is afebrile, with supine systolic blood pressure (BP) ≥ 90 and ≤ 140 mmHg, supine diastolic BP ≥ 50 and ≤ 90 mmHg, and pulse rate ≥ 40 and ≤ 110 bpm at screening.
- Subject has normal or clinically acceptable 12 lead ECG. In addition:
- If female, subject has a QTcF value ≤ 450 msec at screening.
- If male, subject has a QTcF value ≤ 430 msec at screening.
Who cannot join
- The presence of any of the following will exclude a subject from enrollment:
- Subject has any significant medical condition (including but not limited to neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, or other major disorders), laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
- Subject has any condition that confounds the ability to interpret data from the study.
- Female subjects are prohibited from participating in Part 1. Female subjects may participate in Parts 2-3.
- Subject is pregnant or breastfeeding.
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- Subject was exposed to an investigational drug (new chemical entity) within 30 days preceding the first dose administration, or 5 half-lives of that investigational drug, if known (whichever is longer).
- Subject has used any prescribed systemic or topical medication (including but not limited to analgesics, anesthetics, etc) within 30 days prior to the first dose administration, or 5 half-lives of that investigational drug, if known (whichever is longer). Exceptions may apply on a case-by-case basis if considered not to interfere with the study objectives as agreed to by the Investigator and Sponsor's Medical Monitor.
- Subject has used any non-prescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days prior to the first dose administration. Exceptions may apply on a case-by-case basis if considered not to interfere with the study objectives as agreed to by the Investigator and Sponsor's Medical Monitor.
- Subject has used Cytochrome P450 (CYP) 3A inducers and/or inhibitors (including St. John's Wort) within 30 days preceding the first dose administration. The Indiana University (2016) "Cytochrome P450 Drug Interaction Table" should be utilized to determine inducers and/or inhibitors of CYP3A (http://medicine.iupui.edu/clinpharm/ddis/table.aspx). The Sponsor's Medical Monitor or designee should be queried in case of uncertainty.
- Subject has any surgical or medical conditions possibly affecting drug absorption, distribution, metabolism, or excretion, eg, bariatric procedure. Appendectomy and cholecystectomy are acceptable. Other previous surgeries may be acceptable with concurrence of the Sponsor's Medical Monitor.
- Subject donated blood or serum within 8 weeks before the first dose administration to a blood bank or blood donation center.
- Subject has a history of drug abuse (as defined by the current version of the International Classification of Diseases (ICD V11.0)) within 2 years before the first dose administration, or positive drug screening test reflecting consumption of illicit drugs.
- Subject has a history of alcohol abuse (as defined by the NHS alcohol tracker https://www.nhs.uk/live-well/alcohol-support/calculating-alcohol-units/) within 2 years before the first dose administration, or positive alcohol screen.
- Subject is known to have a history of hepatitis B and/or hepatitis C, or have a positive result to the test for human immunodeficiency virus (HIV) antibodies at screening.
- Note: Subjects who received hepatitis B vaccination and who test positive for hepatitis B surface antibody and negative for both hepatitis B surface antigen and hepatitis B core antibody remain eligible for study participation.
- Subject smokes > 10 cigarettes per day, or the equivalent in other tobacco products (self-reported).
- Subject has received immunization with a live or live attenuated vaccine within 2 months prior to the first dose administration or is planning to receive immunization with a live or live attenuated vaccine for 2 months following the last dose administration.
- Subject has a history of Gilbert's syndrome or has laboratory findings at screening that, in the opinion of the Investigator, are indicative of Gilbert's syndrome.
- Subject has a history of incompletely treated Mycobacterium tuberculosis (TB) infection, as indicated by:
- Subject's medical records documenting incomplete treatment for Mycobacterium TB.
- Subject's self-reported history of incomplete treatment for Mycobacterium TB.
- Note: Subjects with a history of TB who have undergone treatment accepted by the local health authorities (documented) may be eligible for study entry.
- Subject is part of the study site staff personnel or a family member of the study site staff.
- Subject has previously been exposed to CC-99677 (eg in a prior clinical trial).
- Subject has a history of photosensitivity to medications.
- Subject has a documented allergy or history of adverse reaction to required medications in the Part for which he/she is seeking to be enrolled, specifically:
- Methotrexate and/or sulfasalazine (or its analogues) for Part 1
- Itraconazole and/or rifampin (or its analogues) for Part 2
- Midazolam and/or digoxin and/or metformin and/or rosuvastatin (or other HMG-CoA reductases i.e. "statins") for Part 3
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Open-label Study in Healthy Adult Subjects to Evaluate Effects of Cytochrome P450 Inhibition and Induction on the Pharmacokinetics of CC-99677 and the Effects of CC-99677 on the Pharmacokinetics of Digoxin, Metformin, Methotrexate, Midazolam, Rosuvastatin, and Sulfasalazine
It is a phase 1, open-label, single-center, three-part study to assess the safety, tolerability, and pharmacokinetics of multiple doses of CC-99677 administered alone or in combination with either methotrexate and sulfasalazine; itraconazole, rifampin, midazolam, or a cocktail of digoxin, metformin, and rosuvastatin in healthy subjects
Read the detailed description
This study will allow investigation of potential drug-drug interaction mediated through cytochrome P450 enzymes and drug transporter proteins. During each part, blood samples will be collected at prespecified times for pharmacokinetic assessments. Subject safety will be monitored throughout the study. There will be approximately 16 subjects enrolled into each part.
- Conditions
- Healthy Volunteer
- Being tested
- CC-99677, Methotrexate, Sulfasalazine, Itraconazole, Rifampin
- Keywords
- Healthy Volunteer, Pharmacokinetics, Safety Tolerability, CC-99677
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CC-99677Drug
CC-99677
MethotrexateDrug
Methotrexate
SulfasalazineDrug
Sulfasalazine
ItraconazoleDrug
Itraconazole
RifampinDrug
Rifampin
MidazolamDrug
Midazolam
DigoxinDrug
Digoxin
MetforminDrug
Metformin
RosuvastatinDrug
Rosuvastatin
| Study group | Role | What they receive |
|---|---|---|
| Part 1: CC-99677 with Methotrexate and Sulfasalazine | Experimental | Fixed-sequence involving CC-99677 + Methotrexate 7.5 mg and sulfasalazine 1000 mg Receives: Drug: CC-99677; Drug: Methotrexate; Drug: Sulfasalazine |
| Part 2: CC-99677 with Itraconazole and Rifampin | Experimental | Fixed-sequence involving CC-99677 + Rifampin 600 mg and Itraconazole 200 mg Receives: Drug: CC-99677; Drug: Itraconazole; Drug: Rifampin |
| Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin | Experimental | Fixed-sequence involving CC-99677 + Midazolam 2 mg, Digoxin 0.25 mg, Metformin 500 mg, and Rosuvastatin 10 mg. Receives: Drug: CC-99677; Drug: Midazolam; Drug: Digoxin; Drug: Metformin; Drug: Rosuvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics-Cmax
Maximum observed plasma concentration
Measured: Up to approximately 72 hours
Pharmacokinetics-AUC0-t
Area under the plasma concentration-time curve from time zero extrapolated to the last quantifiable concentration
Measured: Up to approximately 72 hours
Secondary outcomes (3)
Adverse Events (AEs)
Number of subjects with adverse events
Measured: From enrollment until at least 28 days after completion of treatment
Pharmacokinetics-Cmax
Maximum observed plasma concentrations of metabolites
Measured: Up to approximately 72 hours
Pharmacokinetics-AUC0-t
Ratio of area under the plasma concentration-time curve from time zero extrapolated to the last quantifiable concentration of parent and metabolite
Measured: Up to approximately 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2020
- Study start13 Mar 2020
- Primary completion2 Jun 2021
- Study completion2 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteerStudies of the same condition, open and under way.
- More trials run by CelgeneThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kofi Mensah, MD, PhD, Study director, Celgene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04268394
- Sponsor's protocol ID
- CC-99677-CP-002
- Other IDs
- U1111-1247-0554, 2019-003523-38, 2019
- Status last verified
- Aug 2021
- First submitted
- 11 Feb 2020
- Last updated
- 18 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label Study in Healthy Adult Subjects to Evaluate Effects of Cytochrome P450 Inhibition and Induction on the Pharmacokinetics of CC-99677 and the Effects of CC-99677 on the Pharmacokinetics of Digoxin, Metformin, Methotrexate, Midazolam, Rosuvastatin, and Sulfasalazine
- ClinicalTrials.gov ID
- NCT04268394
- Acronym / sponsor ID
- CC-99677-CP-002
- Conditions
- Healthy Volunteer
- Keywords
- Healthy Volunteer, Pharmacokinetics, Safety Tolerability, CC-99677
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 13 Mar 2020 (actual)
- Primary completion
- 2 Jun 2021 (actual)
- Study completion
- 2 Jun 2021 (actual)
- First posted
- 13 Feb 2020 (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.
It is a phase 1, open-label, single-center, three-part study to assess the safety, tolerability, and pharmacokinetics of multiple doses of CC-99677 administered alone or in combination with either methotrexate and sulfasalazine; itraconazole, rifampin, midazolam, or a cocktail of digoxin, metformin, and rosuvastatin in healthy subjects
Detailed description
This study will allow investigation of potential drug-drug interaction mediated through cytochrome P450 enzymes and drug transporter proteins. During each part, blood samples will be collected at prespecified times for pharmacokinetic assessments. Subject safety will be monitored throughout the study. There will be approximately 16 subjects enrolled into each part.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1: CC-99677 with Methotrexate and Sulfasalazine | Experimental | Drug: CC-99677, Drug: Methotrexate, Drug: SulfasalazineFixed-sequence involving CC-99677 + Methotrexate 7.5 mg and sulfasalazine 1000 mg |
| Part 2: CC-99677 with Itraconazole and Rifampin | Experimental | Drug: CC-99677, Drug: Itraconazole, Drug: RifampinFixed-sequence involving CC-99677 + Rifampin 600 mg and Itraconazole 200 mg |
| Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin | Experimental | Drug: CC-99677, Drug: Midazolam, Drug: Digoxin, Drug: Metformin, Drug: RosuvastatinFixed-sequence involving CC-99677 + Midazolam 2 mg, Digoxin 0.25 mg, Metformin 500 mg, and Rosuvastatin 10 mg. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (21 listed)
- Subject is ≥ 18 and ≤ 64 years of age at the time of signing the informed consent form (ICF).
- Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
- Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
- Subject is in good health, as determined by the Investigator based on a physical examination at screening.
- Female subjects of childbearing potential (FCBP) are not permitted in Part 1, but are permitted in Parts 2 and 3, and must:
Key exclusion criteria (30 listed)
- Subject has any significant medical condition (including but not limited to neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, or other major disorders), laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
- Subject has any condition that confounds the ability to interpret data from the study.
- Female subjects are prohibited from participating in Part 1. Female subjects may participate in Parts 2-3.
- Subject is pregnant or breastfeeding.
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 |
|---|---|---|
| CC-99677CC-99677 | Drug | Part 1: CC-99677 with Methotrexate and Sulfasalazine, Part 2: CC-99677 with Itraconazole and Rifampin, Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin |
| MethotrexateMethotrexate | Drug | Part 1: CC-99677 with Methotrexate and Sulfasalazine |
| SulfasalazineSulfasalazine | Drug | Part 1: CC-99677 with Methotrexate and Sulfasalazine |
| ItraconazoleItraconazole | Drug | Part 2: CC-99677 with Itraconazole and Rifampin |
| RifampinRifampin | Drug | Part 2: CC-99677 with Itraconazole and Rifampin |
| MidazolamMidazolam | Drug | Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin |
| DigoxinDigoxin | Drug | Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin |
| MetforminMetformin | Drug | Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin |
| RosuvastatinRosuvastatin | Drug | Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin |
Primary outcome
Pharmacokinetics-Cmax
Time frame: Up to approximately 72 hours
Maximum observed plasma concentration
Pharmacokinetics-AUC0-t
Time frame: Up to approximately 72 hours
Area under the plasma concentration-time curve from time zero extrapolated to the last quantifiable concentration
3 secondary outcomes
Adverse Events (AEs)
Time frame: From enrollment until at least 28 days after completion of treatment
Pharmacokinetics-Cmax
Time frame: Up to approximately 72 hours
Pharmacokinetics-AUC0-t
Time frame: Up to approximately 72 hours
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 18 Aug 2021.
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Healthy Participants
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.
Kofi Mensah, MD, PhD study director
Celgene
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CC-99677, Methotrexate and Sulfasalazine in people with Healthy Volunteer, run by Celgene at 1 site in United Kingdom.
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 21 inclusion and 30 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 18 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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-Cmax (time frame: Up to approximately 72 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Aug 2021.