Cytomegalovirus (CMV)Phase 1NCT02775240
Study of SHP620 (Maribavir) in Healthy Adults
A Phase 1 study testing Digoxin, Maribavir and Dextromethorphan in people with Cytomegalovirus (CMV), run by Shire at 1 site in United States.
Trial summary
The purpose of this study is to determine how an investigational treatment (maribavir) is handled by the body when administered with two already approved drugs (digoxin and dextromethorphan). Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Cytomegalovirus (CMV)
- What is being tested?
- Digoxin, Maribavir and Dextromethorphan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jul 2016to 12 Sep 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- An understanding, ability, and willingness to fully comply with study procedures and restrictions.
- Ability to provide written, personally signed, and dated informed consent to participate in the study, before completing any study-related procedures.
- Age 18-50 years, inclusive at the time of consent.
- Subjects must be willing to consent to and provide blood samples for pharmacogenomics analysis.
- Willingness to comply with any applicable contraceptive requirements of the protocol and is:
- Male, or
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- Female of non-childbearing potential
- Non-pregnant, non-lactating female
- Females must be at least 90 days postpartum or nulliparous.
- Must be considered "healthy." Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry (includes T3, T4, and TSH at screening only), and urinalysis.
- Body mass index (BMI) between 18.5 and 30.0 kg/m2 inclusive.
- Hemoglobin is equal to or greater than 12.0g/dL.
- Ability to swallow a dose of investigational product (which may be multiple tablets at one time or consecutively 1 tablet at a time)
Who cannot join
- Subject has a clinically significant history or a disorder detected during the medical interview/physical examination such as any cardiovascular, broncho-pulmonary, gastrointestinal (eg, inflammatory bowel disease, chronic diarrhea), hepatic, biliary (including gallbladder removal), renal, hematological, endocrine, autoimmune, neurological, or psychiatric disease (including depression) or any other medical condition that is capable of altering the absorption, metabolism, or elimination of drugs; or of constituting a risk factor when taking the investigational product in the judgment of the investigator.
- Known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients.
- Significant illness, as judged by the investigator, within 2 weeks of the first dose of investigational product.
- Known history of alcohol or other substance abuse within the last year.
- Donation of blood or blood products (eg, plasma or platelets) within 60 days prior to receiving the first dose of investigational product.
- Within 30 days prior to the first dose of investigational product:
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- Have used an investigational product (if elimination half-life is <6 days, otherwise 5 half-lives).
- Have been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this study.
- Have had any substantial changes in eating habits, as assessed by the investigator.
- Confirmed systolic blood pressure >139 mmHg or <89 mmHg and diastolic blood pressure >89 mmHg or <49 mmHg.
- Twelve-lead ECG demonstrating QTcB >450 msec at screening.
- A positive screen for alcohol or drugs of abuse at screening or Day -1, Period 1.
- Male subjects who consume more than 21 units of alcohol per week or 3 units per day; female subjects who consume more than 14 units of alcohol per week or 2 units per day (1 alcohol unit=1 beer or 1 wine [5 oz/150 mL] or 1 liquor [1.5 oz/40 mL] or 0.75 oz alcohol).
- A positive human immunodeficiency virus, hepatitis B surface antibody, or hepatitis C virus antibody screen.
- Use of tobacco in any form (eg, smoking or chewing) or other nicotine-containing products in any form (eg, gum, patch). Ex-users must report that they have stopped using tobacco for at least 30 days prior to receiving the first dose of investigational product.
- Routine consumption of more than 2 units of caffeine per day or subjects who experience caffeine withdrawal headaches. (One caffeine unit is contained in the following items: one 6 oz [180 mL] cup of coffee, two 12 oz [360 mL] cans of cola, one 12 oz cup of tea, or three 1 oz [85 g] chocolate bars. Decaffeinated coffee, tea, or cola are not considered to contain caffeine.)
- Prior screen failure, randomization, participation, or enrollment in this study or prior enrollment in a clinical study investigating maribavir.
- Current use (defined as use within 14 days prior to the first dose of investigational product) of any medication (including over-the-counter, herbal, or homeopathic preparations [eg, St. John's wort, ginkgo biloba]) with the exception of hormonal replacement therapy and occasional use of ibuprofen and acetaminophen.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- Ingestion of known CYP3A modulators within 7 days of Day 1, Period 1 (includes grapefruit or grapefruit juice, oranges, Seville oranges, apples or apple juice, vegetables from the mustard green family [eg, kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard], charbroiled meats, and products containing these ingredients).
Trial locations and contacts
1 site in 1 country.
United States1 site
Clinical Pharmacology of Miami, Inc.
Miami, Florida, 33014
About this study
Official title: A Phase 1, Open-label, 2-period Fixed-sequence Study to Evaluate the Effect of Multiple Doses of SHP620 (Maribavir) on the Pharmacokinetics of Digoxin and Dextromethorphan in Healthy Adult Subjects
The purpose of this study is to determine how an investigational treatment (maribavir) is handled by the body when administered with two already approved drugs (digoxin and dextromethorphan). The study will also look at the safety and tolerability when maribavir is coadministered with digoxin and dextromethorphan versus digoxin and dextromethorphan alone.
- Conditions
- Cytomegalovirus (CMV)
- Being tested
- Digoxin, Maribavir, Dextromethorphan
- Keywords
- Maribavir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DigoxinDrug
0.5 mg (2 x 0.25 mg) Digoxin oral dose
MaribavirDrug
200mg twice a day for 8 days
DextromethorphanDrug
30 mg oral dose
| Study group | Role | What they receive |
|---|---|---|
| Digoxin | Active comparator | On Day 1, subjects will receive a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin. Receives: Drug: Digoxin |
| Maribavir | Experimental | On Day 8 through Day 15, subjects will receive a 400 mg (2 x 200 mg) BID oral dose of maribavir. Subjects will be given the second dose of maribavir approximately 12 hours after the first dose. On Day 13, subjects will receive a coadministration of a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin and a single 30 mg oral dose of dextromethorphan given with the morning dose of maribavir. Receives: Drug: Digoxin; Drug: Maribavir; Drug: Dextromethorphan |
| Dextromethorphan | Active comparator | On Day 1, subjects will receive a single 30 mg oral dose of dextromethorphan. Receives: Drug: Dextromethorphan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Observed Plasma Concentration (Cmax) of Digoxin
Cmax is the maximum observed plasma concentration of digoxin.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Maximum Observed Plasma Concentration (Cmax) of Dextromethorphan
Cmax is the maximum observed plasma concentration of dextromethorphan.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Maximum Observed Plasma Concentration (Cmax) of Dextrorphan
Cmax is the maximum observed plasma concentration of dextrorphan, the metabolite of dextromethorphan.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Maximum Observed Plasma Concentration (Cmax) of Maribavir
Cmax is the maximum observed plasma concentration of maribavir.
Measured: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13
Time to Reach Maximum Plasma Concentration (Tmax) of Digoxin
Tmax is the time to reach the maximum observed drug concentration in plasma during a dosing interval.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Time to Reach Maximum Plasma Concentration (Tmax) of Dextromethorphan
Tmax is the time to reach the maximum observed drug concentration in plasma during a dosing interval.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Time to Reach Maximum Plasma Concentration (Tmax) of Dextrorphan
Tmax is the time to reach the maximum observed drug concentration in plasma during a dosing interval.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Time to Reach Maximum Plasma Concentration (Tmax) of Maribavir
Tmax is the time to reach the maximum observed drug concentration in plasma during a dosing interval.
Measured: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Digoxin
AUC0-infinity is the area under the plasma concentration versus time curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextromethorphan
AUC0-infinity is the area under the plasma concentration versus time curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextrorphan
AUC0-infinity is the area under the plasma concentration versus time curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Digoxin
AUClast is the area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Dextromethorphan
AUClast is the area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Dextrorphan
AUClast is the area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Parent/Metabolite Ratio of Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) for Dextromethorphan Over AUClast for Dextrorphan (AUClast Parent/Metabolite Ratio)
AUClast parent/metabolite ratio is the ratio of AUClast for dextromethorphan over AUClast for dextrorphan.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Parent/Metabolite Ratio of Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) for Dextromethorphan Over AUC0-infinity for Dextrorphan (AUC0-infinity Parent/Metabolite Ratio)
AUC0-infinity parent/metabolite ratio is the ratio of AUC0-infinity for dextromethorphan over AUC0-infinity for dextrorphan.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the End of the Dosing Interval at Steady-State (AUCtau) of Maribavir
AUCtau is the area under the plasma concentration versus time curve from the time zero to the end of the dosing interval at steady-state.
Measured: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13
First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Digoxin
Lambda z is the first-order rate constant associated with the terminal (log-linear) portion of the plasma concentration versus time curve, determined as the negative slope of the terminal log-linear phase of the curve.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextromethorphan
Lambda z is the first-order rate constant associated with the terminal (log-linear) portion of the plasma concentration versus time curve, determined as the negative slope of the terminal log-linear phase of the curve.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextrorphan
Lambda z is the first-order rate constant associated with the terminal (log-linear) portion of the plasma concentration versus time curve, determined as the negative slope of the terminal log-linear phase of the curve.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Terminal Half-life (t1/2) of Digoxin
Terminal half-life (t1/2) is the time in hours required for the concentration of the drug to reach half of its original value.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Terminal Half-life (t1/2) of Dextromethorphan
Terminal half-life (t1/2) is the time in hours required for the concentration of the drug to reach half of its original value.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Terminal Half-life (t1/2) of Dextrorphan
Terminal half-life (t1/2) is the time in hours required for the concentration of the drug to reach half of its original value.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Terminal Half-life (t1/2) of Maribavir
Terminal half-life (t1/2) is the time in hours required for the concentration of the drug to reach half of its original value.
Measured: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13
Apparent Oral Clearance (CL/F) of Digoxin
CL/F is equal to dose/AUC0-infinity (dose divided by area under the plasma concentration versus time curve extrapolated to infinity [AUC0-infinity]).
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Apparent Oral Clearance (CL/F) of Dextromethorphan
CL/F is equal to dose/AUC0-infinity (dose divided by area under the plasma concentration versus time curve extrapolated to infinity [AUC0-infinity])
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Apparent Oral Clearance (CL/F) of Maribavir
CL/F is equal to dose/AUCtau (dose divided by area under the curve from time 0 to the end of the dosing interval at steady state [AUCtau])
Measured: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13
Concentration at the End of Dosing Interval (Ctau) of Maribavir
Ctau is the concentration of maribavir at the end of the dosing interval.
Measured: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13
Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Digoxin
Vz/F is the volume of distribution associated with the terminal slope following extravascular administration divided by the fraction of dose absorbed.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan
Vz/F is the volume of distribution associated with the terminal slope following extravascular administration divided by the fraction of dose absorbed.
Measured: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Pre-dose Concentration (C0) of Maribavir
C0 is the lowest concentration reached by a drug before the next dose is administered.
Measured: Pre-dose on Day 13
Secondary outcomes (2)
Number of Participants With Study-related Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence in a participant administered an investigational product (IP) and that did not necessarily have a causal relationship with this treatment. AE was considered to be study-related if there was any valid reason, even if undetermined or untested, for suspecting a possible cause-and-effect relationship between the IP and the occurrence of the AE. An AE was considered a TEAE if it had a start date on or after the first dose of IP or if it had a start date before the date of the first dose of IP, but increased in intensity on or after the date of the first dose of IP. A serious adverse event (SAE) was any untoward medical occurrence (related either to the test product or to the other IP or not) that at any dose resulted in death; was life-threatening; required or prolongation of hospitalization; resulted in persistent or significant disability/incapacity; was a congenital abnormality/birth defect; was an important medical event.
Measured: From start of study drug administration up to follow-up (up to 25 days)
Number of Participants With Clinically Significant Changes Reported as TEAE in Physical Examination, Vital Signs, 12-lead ECGs, Hematology, Blood Chemistry and Urinalysis
Clinical significance of the changes observed in the safety parameters to be reported as TEAE was interpreted by the investigator.
Measured: Baseline up to Day 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2016 (estimated)
- Study start21 Jul 2016
- Primary completion12 Sep 2016
- Study completion12 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus (CMV)Studies 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02775240
- Sponsor's protocol ID
- SHP620-115
- Status last verified
- May 2021
- First submitted
- 20 Apr 2016
- Last updated
- 3 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Publications
Song IH, Ilic K, Murphy J, Lasseter K, Martin P. Effects of Maribavir on P-Glycoprotein and CYP2D6 in Healthy Volunteers. J Clin Pharmacol. 2020 Jan;60(1):96-106. doi: 10.1002/jcph.1504. Epub 2019 Aug 6.
PubMed 31385617
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, 2-period Fixed-sequence Study to Evaluate the Effect of Multiple Doses of SHP620 (Maribavir) on the Pharmacokinetics of Digoxin and Dextromethorphan in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT02775240
- Acronym / sponsor ID
- SHP620-115
- Conditions
- Cytomegalovirus (CMV)
- Keywords
- Maribavir
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 21 Jul 2016 (actual)
- Primary completion
- 12 Sep 2016 (actual)
- Study completion
- 12 Sep 2016 (actual)
- First posted
- 17 May 2016 (estimated)
- Results
- Posted 16 Jan 2019
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 determine how an investigational treatment (maribavir) is handled by the body when administered with two already approved drugs (digoxin and dextromethorphan). The study will also look at the safety and tolerability when maribavir is coadministered with digoxin and dextromethorphan versus digoxin and dextromethorphan alone.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Digoxin | Active comparator | Drug: DigoxinOn Day 1, subjects will receive a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin. |
| Maribavir | Experimental | Drug: Digoxin, Drug: Maribavir, Drug: DextromethorphanOn Day 8 through Day 15, subjects will receive a 400 mg (2 x 200 mg) BID oral dose of maribavir. Subjects will be given the second dose of maribavir approximately 12 hours after the first dose. On Day 13, subjects will receive a coadministration of a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin and a single 30 mg oral dose of dextromethorphan given with the morning dose of maribavir. |
| Dextromethorphan | Active comparator | Drug: DextromethorphanOn Day 1, subjects will receive a single 30 mg oral dose of dextromethorphan. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- An understanding, ability, and willingness to fully comply with study procedures and restrictions.
- Ability to provide written, personally signed, and dated informed consent to participate in the study, before completing any study-related procedures.
- Age 18-50 years, inclusive at the time of consent.
- Subjects must be willing to consent to and provide blood samples for pharmacogenomics analysis.
- Willingness to comply with any applicable contraceptive requirements of the protocol and is:
Key exclusion criteria (20 listed)
- Subject has a clinically significant history or a disorder detected during the medical interview/physical examination such as any cardiovascular, broncho-pulmonary, gastrointestinal (eg, inflammatory bowel disease, chronic diarrhea), hepatic, biliary (including gallbladder removal), renal, hematological, endocrine, autoimmune, neurological, or psychiatric disease (including depression) or any other medical condition that is capable of altering the absorption, metabolism, or elimination of drugs; or of constituting a risk factor when taking the investigational product in the judgment of the investigator.
- Known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients.
- Significant illness, as judged by the investigator, within 2 weeks of the first dose of investigational product.
- Known history of alcohol or other substance abuse within the last year.
- Donation of blood or blood products (eg, plasma or platelets) within 60 days prior to receiving the first dose of investigational product.
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 |
|---|---|---|
| Digoxin0.5 mg (2 x 0.25 mg) Digoxin oral dose | Drug | Digoxin, Maribavir |
| Maribavir200mg twice a day for 8 days | Drug | Maribavir |
| Dextromethorphan30 mg oral dose | Drug | Dextromethorphan, Maribavir |
Primary outcome
Maximum Observed Plasma Concentration (Cmax) of Digoxin
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Cmax is the maximum observed plasma concentration of digoxin.
Maximum Observed Plasma Concentration (Cmax) of Dextromethorphan
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Cmax is the maximum observed plasma concentration of dextromethorphan.
Maximum Observed Plasma Concentration (Cmax) of Dextrorphan
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Cmax is the maximum observed plasma concentration of dextrorphan, the metabolite of dextromethorphan.
Maximum Observed Plasma Concentration (Cmax) of Maribavir
Time frame: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13
Cmax is the maximum observed plasma concentration of maribavir.
Time to Reach Maximum Plasma Concentration (Tmax) of Digoxin
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Tmax is the time to reach the maximum observed drug concentration in plasma during a dosing interval.
Time to Reach Maximum Plasma Concentration (Tmax) of Dextromethorphan
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Tmax is the time to reach the maximum observed drug concentration in plasma during a dosing interval.
Time to Reach Maximum Plasma Concentration (Tmax) of Dextrorphan
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Tmax is the time to reach the maximum observed drug concentration in plasma during a dosing interval.
Time to Reach Maximum Plasma Concentration (Tmax) of Maribavir
Time frame: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13
Tmax is the time to reach the maximum observed drug concentration in plasma during a dosing interval.
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Digoxin
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
AUC0-infinity is the area under the plasma concentration versus time curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration.
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextromethorphan
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
AUC0-infinity is the area under the plasma concentration versus time curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration.
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextrorphan
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
AUC0-infinity is the area under the plasma concentration versus time curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration.
Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Digoxin
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
AUClast is the area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration.
Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Dextromethorphan
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
AUClast is the area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration.
Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Dextrorphan
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
AUClast is the area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration.
Parent/Metabolite Ratio of Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) for Dextromethorphan Over AUClast for Dextrorphan (AUClast Parent/Metabolite Ratio)
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
AUClast parent/metabolite ratio is the ratio of AUClast for dextromethorphan over AUClast for dextrorphan.
Parent/Metabolite Ratio of Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) for Dextromethorphan Over AUC0-infinity for Dextrorphan (AUC0-infinity Parent/Metabolite Ratio)
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
AUC0-infinity parent/metabolite ratio is the ratio of AUC0-infinity for dextromethorphan over AUC0-infinity for dextrorphan.
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the End of the Dosing Interval at Steady-State (AUCtau) of Maribavir
Time frame: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13
AUCtau is the area under the plasma concentration versus time curve from the time zero to the end of the dosing interval at steady-state.
First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Digoxin
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Lambda z is the first-order rate constant associated with the terminal (log-linear) portion of the plasma concentration versus time curve, determined as the negative slope of the terminal log-linear phase of the curve.
First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextromethorphan
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Lambda z is the first-order rate constant associated with the terminal (log-linear) portion of the plasma concentration versus time curve, determined as the negative slope of the terminal log-linear phase of the curve.
First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextrorphan
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Lambda z is the first-order rate constant associated with the terminal (log-linear) portion of the plasma concentration versus time curve, determined as the negative slope of the terminal log-linear phase of the curve.
Terminal Half-life (t1/2) of Digoxin
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Terminal half-life (t1/2) is the time in hours required for the concentration of the drug to reach half of its original value.
Terminal Half-life (t1/2) of Dextromethorphan
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Terminal half-life (t1/2) is the time in hours required for the concentration of the drug to reach half of its original value.
Terminal Half-life (t1/2) of Dextrorphan
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Terminal half-life (t1/2) is the time in hours required for the concentration of the drug to reach half of its original value.
Terminal Half-life (t1/2) of Maribavir
Time frame: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13
Terminal half-life (t1/2) is the time in hours required for the concentration of the drug to reach half of its original value.
Apparent Oral Clearance (CL/F) of Digoxin
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
CL/F is equal to dose/AUC0-infinity (dose divided by area under the plasma concentration versus time curve extrapolated to infinity [AUC0-infinity]).
Apparent Oral Clearance (CL/F) of Dextromethorphan
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
CL/F is equal to dose/AUC0-infinity (dose divided by area under the plasma concentration versus time curve extrapolated to infinity [AUC0-infinity])
Apparent Oral Clearance (CL/F) of Maribavir
Time frame: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13
CL/F is equal to dose/AUCtau (dose divided by area under the curve from time 0 to the end of the dosing interval at steady state [AUCtau])
Concentration at the End of Dosing Interval (Ctau) of Maribavir
Time frame: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13
Ctau is the concentration of maribavir at the end of the dosing interval.
Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Digoxin
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Vz/F is the volume of distribution associated with the terminal slope following extravascular administration divided by the fraction of dose absorbed.
Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan
Time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
Vz/F is the volume of distribution associated with the terminal slope following extravascular administration divided by the fraction of dose absorbed.
Pre-dose Concentration (C0) of Maribavir
Time frame: Pre-dose on Day 13
C0 is the lowest concentration reached by a drug before the next dose is administered.
2 secondary outcomes
Number of Participants With Study-related Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs)
Time frame: From start of study drug administration up to follow-up (up to 25 days)
Number of Participants With Clinically Significant Changes Reported as TEAE in Physical Examination, Vital Signs, 12-lead ECGs, Hematology, Blood Chemistry and Urinalysis
Time frame: Baseline up to Day 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31385617Song IH, Ilic K, Murphy J, Lasseter K, Martin P. Effects of Maribavir on P-Glycoprotein and CYP2D6 in Healthy Volunteers. J Clin Pharmacol. 2020 Jan;60(1):96-106. doi: 10.1002/jcph.1504. Epub 2019 Aug 6.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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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.
Study Director study director
Takeda
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 Digoxin, Maribavir and Dextromethorphan in people with Cytomegalovirus (CMV), run by Shire 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 13 inclusion and 20 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 3 Jun 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 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?
Yes. Results are posted in the registry (first posted 16 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximum Observed Plasma Concentration (Cmax) of Digoxin (time frame: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B). The study lists 31 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 NCT02775240, 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 3 Jun 2021.