Drug Interaction StudyPhase 1NCT02807051
To Evaluate the Effect of Clarithromycin on the Systemic Exposure of Pacritinib in Healthy Subjects
A Phase 1 study testing Pacritinib, Clarithromycin and Pacritinib and Clarithromycin in people with Drug Interaction Study, run by CTI BioPharma at 1 site in United States.
Trial summary
This will be an open-label, single-center, crossover, one-way, drug-interaction study to evaluate the effect of 500 mg clarithromycin BID (dosed to steady state) on the PK of a single 400-mg dose of pacritinib in healthy male and female subjects. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Interaction Study
- What is being tested?
- Pacritinib, Clarithromycin and Pacritinib and Clarithromycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to Oct 2014
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- males or females, between 18 and 55 years of age, inclusive;
- BMI between 18.5 and 32.0 kg/m2, inclusive;
- in good health, determined by no clinically significant findings from medical history, physical examination, and vital signs;
- clinical laboratory evaluations (including clinical chemistry panel [fasted at least 10 hours], CBC, and UA) within the reference range for the test laboratory, unless deemed not clinically significant by the Investigator;
- negative test for selected drugs of abuse (including alcohol) at Screening and at Check-in;
- negative hepatitis panel (including hepatitis B surface antigen [HBsAg] and hepatitis C virus antibody [anti-HCV]) and negative HIV antibody screens;
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- females of childbearing potential must be non-pregnant and non-lactating, and agree to use contraception from the time of signing the informed consent or 10 days prior to Check-in (Day -1) until 30 days after the final dose administration. One of the following forms of contraception must be used from the time of signing the informed consent or 10 days prior to Check-in (Day -1) until 30 days after the final dose administration: non-hormonal intrauterine device (IUD) with spermicide; female condom with spermicide; contraceptive sponge with spermicide; intravaginal system (eg, NuvaRing®); diaphragm with spermicide; cervical cap with spermicide; male sexual partner who agrees to use a male condom with spermicide; sterile sexual partner; or abstinence. Oral, implantable, transdermal, or injectable hormonal contraceptives may not be used from the time of signing the informed consent or 10 days prior to Check-in (Day -1) until 14 days after the final dose administration. For all females, the pregnancy test result must be negative at Screening and Check-in (Day -1). Females not of childbearing potential must be postmenopausal for at least 1 year or surgically sterile (eg, tubal ligation, hysterectomy) for at least 90 days;
- males will either be surgically sterile (ie, vasectomy, documented in the medical record by a physician) or agree to use from Check-in (Day -1) until 90 days following Study Completion (Day 19)/ET, one of the following approved methods of contraception: male condom with spermicide; sterile sexual partner; or use by female sexual partner of an IUD with spermicide, a female condom with spermicide, a contraceptive sponge with spermicide, an intravaginal system, a diaphragm with spermicide, a cervical cap with spermicide, or oral, implantable, transdermal, or injectable contraceptives. Subjects must agree to refrain from sperm donation from Check-in (Day -1) until 90 days following Study Completion (Day 19)/ET;
- able to comprehend and willing to sign an Informed Consent Form (ICF).
Who cannot join
- history or clinical manifestation of clinically significant cardiovascular, pulmonary, hepatic (eg, hepatitis), renal, hematologic, gastrointestinal (eg, celiac disease, peptic ulcer, gastroesophageal reflux, inflammatory bowel disease), metabolic, allergic, dermatological, neurological, or psychiatric disorder (as determined by the Investigator; appendectomy and cholecystectomy are not considered to be clinically significant disease);
- abnormalities in liver function tests (any/all of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase >1.5 × upper limit of normal [ULN]; gamma-glutamyl transferase >2 × ULN; or total bilirubin >1.3 × ULN) or kidney function tests (serum creatinine > ULN) that are considered clinically significant by the Investigator, in consultation with the Sponsor;
- history of malignancy, except the following; cancers determined to be cured or in remission for ≥5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps;
- history of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, including clarithromycin, unless approved by the Investigator;
- history of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs except that appendectomy and hernia repair will be allowed;
- history of Gilbert's Syndrome;
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- history or presence of an abnormal ECG, which, in the Investigator's opinion, is clinically significant; QTcF >450 msec, or factors that increase risk for QTc interval prolongation (eg, heart failure, hypokalemia [defined as serum potassium <3.0 mEq/L that is persistent and refractory to correction], or family history of long QT interval syndrome)
- history of alcoholism or drug addiction within 1 year prior to Check-in (Day -1);
- use of tobacco- or nicotine-containing products within 6 months prior to Check-in (Day -1) and during the entire study;
- consumption of alcohol- or caffeine-containing foods and beverages for 72 hours prior to Screening and during the entire study;
- consumption of grapefruit-containing foods and beverages or other CYP3A4 inhibitors or inducers for 72 hours prior to Screening and during the entire study
- participation in any other investigational drug trial in which receipt of an investigational study drug occurred within 5 half-lives or 30 days prior to Check-in (Day -1), whichever is longer;
- use of oral, implantable, injectable, or transdermal hormonal contraceptives within 10 days prior to Check-in (Day -1) or from the time of signing the informed consent (females only) until 14 days after the final dose administration;
- use of any prescription medications and/or products within 14 days prior to Check-in (Day -1) and during the entire study, unless deemed acceptable by the Investigator in consultation with the Sponsor;
- use of any over-the-counter, non-prescription preparations (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days prior to Check-in (Day -1) and during the entire study, unless deemed acceptable by the Investigator;
- poor peripheral venous access;
- donation of blood from 30 days prior to Screening through Study Completion (Day 19)/ET, inclusive, or of plasma from 2 weeks prior to Screening through Study Completion (Day 19)/ET, inclusive;
- receipt of blood products within 2 months prior to Check-in (Day -1);
- any acute or chronic condition that, in the opinion of the Investigator, would limit the subject's ability to complete and/or participate in this clinical study
Trial locations and contacts
1 site in 1 country.
United States1 site
Covance Clinical Research Unit
Daytona Beach, Florida, 32117
About this study
Official title: A Phase 1, Open-Label, Drug-Interaction Study to Evaluate the Effect of Clarithromycin, a Potent CYP3A4 Inhibitor, on the Systemic Exposure of Pacritinib in Healthy Subjects
This will be an open-label, single-center, crossover, one-way, drug-interaction study to evaluate the effect of 500 mg clarithromycin BID (dosed to steady state) on the PK of a single 400-mg dose of pacritinib in healthy male and female subjects.
Read the detailed description
This was a single-center, open-label, one-way crossover, drug-interaction study. On Day 1, subjects received a single oral 400-mg dose of pacritinib. On Day 8 through the morning of Day 12, following a 7-day washout period, 500-mg oral doses of clarithromycin were administered twice daily (BID), 8 to 12 hours apart. It was anticipated that steady-state concentrations of clarithromycin would be achieved by Day 12. On Day 12, a single oral 400-mg dose of pacritinib was co-administered with the final 500-mg dose of clarithromycin.
- Conditions
- Drug Interaction Study
- Being tested
- Pacritinib, Clarithromycin, Pacritinib and Clarithromycin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PacritinibDrug
Also called Pacritinib 100mg
Single 400-mg dose (four 100-mg capsules) administered in the morning on Days 1 and 12
ClarithromycinDrug
Also called Clarithromycin 500mg
Twice-daily, 500-mg dose (one 500-mg tablet) administered every 8 to 12 hours on Day 8 through the morning of Day 12
Pacritinib and ClarithromycinDrug
Also called Pacritinib 100mg and Clarithromycin 500mg
On Day 12, a single oral 400-mg dose of pacritinib was co-administered with the final 500-mg dose of clarithromycin
| Study group | Role | What they receive |
|---|---|---|
| Pacritinib and Clarithromycin | Experimental | Single 400-mg (four 100-mg capsules; lot number 21341) oral doses of pacritinib were administered in the fasted state on Days 1 and 12. Twice daily, 500-mg (1 tablet) oral doses of clarithromycin were administered with or without food on Days 8 through 11 and in the fasted state on the morning of Day 12 Receives: Drug: Pacritinib; Drug: Clarithromycin; Drug: Pacritinib and Clarithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimate ratios of geometric mean values and the corresponding 90% confidence intervals (CIs) for pacritinib treatments with and without clarithromycin
To estimate ratios of geometric mean values and the corresponding 90% confidence intervals
Measured: Fifteen days approximately
Secondary outcomes (8)
Incidence of Treatment-Emergent Adverse Events
To evaluate the safety of pacritinib and tolerability of a single 400 mg dose of pacritinib in patients with hepatic impairment. Safety endpoints for this study include AEs, vital signs, clinical laboratory evaluations, physical examinations, and single 12-lead ECGs
Measured: from Day 1 to Day 19
The apparent terminal elimination rate constant (λZ) and the respective apparent terminal elimination half-life (t½).
Measured: Plasma (Day 1 and 12): 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The maximum plasma concentration (Cmax).
To characterize the pharmacokinetic (PK) profile of pacritinib and its major human metabolites following single-dose administration with and without concomitant clarithromycin in healthy subjects
Measured: Plasma (Day 1 and 12): 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The time to reach maximum plasma concentration (tmax).
To characterize the pharmacokinetic (PK) profile of pacritinib and its major human metabolites following single-dose administration with and without concomitant clarithromycin in healthy subjects
Measured: Plasma (Day 1 and 12): 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The area under the plasma concentration-time curve from time zero to time of the last measured concentration above the limit of quantification (AUC0-t)
To characterize the pharmacokinetic (PK) profile of pacritinib and its major human metabolites following single-dose administration with and without concomitant clarithromycin in healthy subjects
Measured: Plasma (Day 1 and 12): 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The area under the plasma concentration-time curve from zero to infinity (AUC0-∞).
Measured: Plasma (Day 1 and 12): 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The apparent volume of distribution (Vd).
Measured: Plasma (Day 1 and 12): 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The apparent total body clearance (CL/F).
Measured: Plasma (Day 1 and 12): 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2016 (estimated)
- Study startSep 2014
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug Interaction StudyStudies of the same condition, open and under way.
- 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- CTI BioPharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Covance
- Responsible party
- Sponsor
- Investigators
- Frank Farmer, MD, PhD, Principal investigator, Covance
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02807051
- Sponsor's protocol ID
- PAC104
- Status last verified
- Jan 2020
- First submitted
- 3 May 2016
- Last updated
- 29 Jan 2020
- Results posted
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Drug-Interaction Study to Evaluate the Effect of Clarithromycin, a Potent CYP3A4 Inhibitor, on the Systemic Exposure of Pacritinib in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02807051
- Acronym / sponsor ID
- PAC104
- Conditions
- Drug Interaction Study
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- CTI BioPharmaIndustry (pharma, biotech, devices)
- Collaborators
- Covance
- Study start
- Sep 2014
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 21 Jun 2016 (estimated)
- 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.
This will be an open-label, single-center, crossover, one-way, drug-interaction study to evaluate the effect of 500 mg clarithromycin BID (dosed to steady state) on the PK of a single 400-mg dose of pacritinib in healthy male and female subjects.
Detailed description
This was a single-center, open-label, one-way crossover, drug-interaction study. On Day 1, subjects received a single oral 400-mg dose of pacritinib. On Day 8 through the morning of Day 12, following a 7-day washout period, 500-mg oral doses of clarithromycin were administered twice daily (BID), 8 to 12 hours apart. It was anticipated that steady-state concentrations of clarithromycin would be achieved by Day 12. On Day 12, a single oral 400-mg dose of pacritinib was co-administered with the final 500-mg dose of clarithromycin.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pacritinib and Clarithromycin | Experimental | Drug: Pacritinib, Drug: Clarithromycin, Drug: Pacritinib and ClarithromycinSingle 400-mg (four 100-mg capsules; lot number 21341) oral doses of pacritinib were administered in the fasted state on Days 1 and 12. Twice daily, 500-mg (1 tablet) oral doses of clarithromycin were administered with or without food on Days 8 through 11 and in the fasted state on the morning of Day 12 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- males or females, between 18 and 55 years of age, inclusive;
- BMI between 18.5 and 32.0 kg/m2, inclusive;
- in good health, determined by no clinically significant findings from medical history, physical examination, and vital signs;
- clinical laboratory evaluations (including clinical chemistry panel [fasted at least 10 hours], CBC, and UA) within the reference range for the test laboratory, unless deemed not clinically significant by the Investigator;
- negative test for selected drugs of abuse (including alcohol) at Screening and at Check-in;
Key exclusion criteria (19 listed)
- history or clinical manifestation of clinically significant cardiovascular, pulmonary, hepatic (eg, hepatitis), renal, hematologic, gastrointestinal (eg, celiac disease, peptic ulcer, gastroesophageal reflux, inflammatory bowel disease), metabolic, allergic, dermatological, neurological, or psychiatric disorder (as determined by the Investigator; appendectomy and cholecystectomy are not considered to be clinically significant disease);
- abnormalities in liver function tests (any/all of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase >1.5 × upper limit of normal [ULN]; gamma-glutamyl transferase >2 × ULN; or total bilirubin >1.3 × ULN) or kidney function tests (serum creatinine > ULN) that are considered clinically significant by the Investigator, in consultation with the Sponsor;
- history of malignancy, except the following; cancers determined to be cured or in remission for ≥5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps;
- history of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, including clarithromycin, unless approved by the Investigator;
- history of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs except that appendectomy and hernia repair will be allowed;
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 |
|---|---|---|
| PacritinibAlso: Pacritinib 100mgSingle 400-mg dose (four 100-mg capsules) administered in the morning on Days 1 and 12 | Drug | Pacritinib and Clarithromycin |
| ClarithromycinAlso: Clarithromycin 500mgTwice-daily, 500-mg dose (one 500-mg tablet) administered every 8 to 12 hours on Day 8 through the morning of Day 12 | Drug | Pacritinib and Clarithromycin |
| Pacritinib and ClarithromycinAlso: Pacritinib 100mg and Clarithromycin 500mgOn Day 12, a single oral 400-mg dose of pacritinib was co-administered with the final 500-mg dose of clarithromycin | Drug | Pacritinib and Clarithromycin |
Primary outcome
Estimate ratios of geometric mean values and the corresponding 90% confidence intervals (CIs) for pacritinib treatments with and without clarithromycin
Time frame: Fifteen days approximately
To estimate ratios of geometric mean values and the corresponding 90% confidence intervals
8 secondary outcomes
Incidence of Treatment-Emergent Adverse Events
Time frame: from Day 1 to Day 19
The apparent terminal elimination rate constant (λZ) and the respective apparent terminal elimination half-life (t½).
Time frame: Plasma (Day 1 and 12): 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The maximum plasma concentration (Cmax).
Time frame: Plasma (Day 1 and 12): 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The time to reach maximum plasma concentration (tmax).
Time frame: Plasma (Day 1 and 12): 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The area under the plasma concentration-time curve from time zero to time of the last measured concentration above the limit of quantification (AUC0-t)
Time frame: Plasma (Day 1 and 12): 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The area under the plasma concentration-time curve from zero to infinity (AUC0-∞).
Time frame: Plasma (Day 1 and 12): 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The apparent volume of distribution (Vd).
Time frame: Plasma (Day 1 and 12): 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The apparent total body clearance (CL/F).
Time frame: Plasma (Day 1 and 12): 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs 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 29 Jan 2020.
- Individual participant dataSharing planned: Yes
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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.
Frank Farmer, MD, PhD principal investigator
Covance
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 Pacritinib, Clarithromycin and Pacritinib and Clarithromycin in people with Drug Interaction Study, run by CTI BioPharma at 1 site 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 9 inclusion and 19 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 29 Jan 2020. 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 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?
Estimate ratios of geometric mean values and the corresponding 90% confidence intervals (CIs) for pacritinib treatments with and without clarithromycin (time frame: Fifteen days approximately). 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 29 Jan 2020.