HealthyPhase 1NCT02473627

A PHASE 1, OPEN-LABEL, CROSS-OVER, FIXED SEQUENCE STUDY TO EVALUATE THE EFFECT OF MULTIPLE DOSES OF DS-1971A ON THE SINGLE DOSE PHARMACOKINETICS OF PROBE SUBSTRATES FOR CYP2B6, CYP2C8, CYP2C9, CYP2C19 AND CYP3A4 ENZYMES IN HEALTHY MALE AND FEMALE SUBJECTS

A Phase 1 study testing DS-1971a, midazolam hydrochloride and Omeprazole in people with Healthy, run by Daiichi Sankyo at 1 site in United Kingdom.

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 an open-label, cross-over, fixed-sequence study. All subjects will receive the same treatment in two study periods. The study is designed to test whether DS-1971a has any effect on the activity of various enzymes involved in the metabolism of medicines, using test medications. Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: DS-1971a, midazolam hydrochloride and Omeprazole
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 Kingdom
Study dates: May 2015to Jul 2015
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 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Male or female aged 18 to 65 years, inclusive.
Be in good general health as determined by medical history, physical examination and Screening investigations, and be taking no regular medication.
A body mass index (BMI) in the range 18 to 30 kg/m2, inclusive, and weighing between 50 and 100 kg, inclusive. BMI is calculated as weight [kg]/(height [m])*2.
Female subjects must be of nonchildbearing potential as follows:
Must be postmenopausal (the last menstrual period was at least 12 months before Screening, and a follicle stimulating hormone [FSH] test at Screening confirms postmenopausal status); or Must be surgically sterile having undergone hysterectomy, bilateral oophorectomy, bilateral salpingectomy and/or bilateral tubal ligation.
Willing to comply with all study restrictions, including the use of contraception, concomitant medication and dietary and lifestyle restrictions.

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Possessing sufficient intelligence to understand the nature of the study and any hazards of participating in it, and the ability to communicate satisfactorily with the Investigator and to participate in, and comply with the requirements of, the entire study.
Have given written consent to participate after reading the ICF, and after having the opportunity to discuss the study with the Investigator or his/her delegate.
Have given written consent to have his/her data entered into The Overvolunteering Prevention System.

Who cannot join

Clinically relevant abnormal history, physical findings, ECG findings or laboratory values that could interfere with the objectives of the study or the safety of the subject.
Presence of history of acute or chronic illness, including (but not limited to) liver or kidney disease, hypertension, seizures, or any known impairment of endocrine, or other specific body-organ dysfunction.
Presence or history of severe adverse reaction to any medicine.
Presence or history of malignant disease.
Acute or chronic infectious disease, including human immunodeficiency virus (HIV), hepatitis B virus or C virus (HCV) infection.
Surgery (eg, stomach bypass) or medical condition that might affect absorption of medicines.

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Significant illness within 4 weeks before the dose of study medication.
Participation in another clinical trial of a new chemical entity or a prescription medicine within the previous 3 months, or unwilling to abstain from participating in other clinical trials during the study and for 3 months after receipt of study medication.
Participation in another clinical study with DS-1971a.
Blood pressure (BP) and heart rate in semisupine position at the Screening examination outside the ranges 90 to 140 mmHg systolic, 40 to 90 mmHg diastolic; heart rate 40 to 100 beats/min. Subjects with Stage 1 hypertension (systolic 140 to 160 mmHg; diastolic 90 to 100 mmHg) may be enrolled provided they do not have evidence of end-organ damage, diabetes or a 10 year cardiovascular risk > 20%.
Abnormal ECG waveform morphology at Screening that would preclude accurate measurement of the uncorrected QT interval (QT) duration.
QT interval for heart rate corrected using Fridericia's formula (QTcF) interval duration > 430 msec for men or > 450 msec for women, obtained as an average from the measurements on duplicate Screening ECGs.
Estimated glomerular filtration rate (eGFR) < 80 mL/min/1.73 m*2 or an absolute creatinine value above the upper limit of the normal range. eGFR will be estimated at Screening using the Modification of Diet in Renal Disease (MDRD) equation.
Poor metaboliser genotype status for CYP2C9 and CYP2C19 (Note: this exclusion criterion is to ensure that the study population is sensitive to a metabolic interaction).
Use of any prescription medicine, over the counter (OTC) medications, herbal remedies (such as St John's Wort), or food known to be strong inhibitors or strong inducers of CYP enzymes (also known as CYP450 enzymes) during the 30 days before the dose of study medication; use of any other prescription or OTC medicine, including dietary supplements or herbal remedies, during the 7 days before the first dose of study medication.
Consumption of certain foods or beverages before the dose and throughout the study period.
Loss of more than 400 mL blood plasma, platelets or any other blood components during the 3 months before the first dose of study medication, or unwilling to abstain from doing so during the study and for 3 months after receipt of study medication.
Abuse of drugs or alcohol in the past, or intake of more than 21 units of alcohol weekly (for men) or 14 units of alcohol weekly (for women).
Use of tobacco products or nicotine containing products during the 3 months before the dose of study medication.
Likely possibility that the subject will not cooperate with the requirements of the protocol.
Objection by General Practitioner to subjects entering the study.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Study site
London, NW10 7EW

Other trials in United Kingdom

About this study

Conditions: Healthy
Being tested: DS-1971a, midazolam hydrochloride, Omeprazole, Pioglitazone hydrochloride, Buproprion
Keywords: Pharmacokinetics

What participants receive

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

DS-1971aDrug
200mg tablet
midazolam hydrochlorideDrug
2.5mg oromucosal liquid
OmeprazoleDrug
20mg gastro-resistant capsule
Pioglitazone hydrochlorideDrug
15mg tablet
BuproprionDrug
150mg Prolonged release tablet
TolbutamideDrug
500mg tablet

Study groups in NCT02473627
Study group	Role	What they receive
Period 1	Experimental	Period 1 Day 1: single oral dose of 2.5 mg midazolam hydrochloride Day 2: single oral cocktail dose of 20 mg omeprazole, 15 mg pioglitazone hydrochloride, 500 mg tolbutamide and 150 mg bupropion Receives: Drug: midazolam hydrochloride; Drug: Omeprazole; Drug: Pioglitazone hydrochloride; Drug: Buproprion; Drug: Tolbutamide
Period 2	Experimental	Period 2 Days 1 through 12 repeated doses of 400 mg DS-1971a administered orally bid . On the days listed below, each probe substrate(s) will be coadministered with the morning dose of DS 1971a: Day 8: single oral dose of 2.5 mg midazolam hydrochloride Day 9: single oral cocktail dose of 20 mg omeprazole, 15 mg pioglitazone hydrochloride, 500 mg tolbutamide and 150 mg bupropion Receives: Drug: DS-1971a; Drug: midazolam hydrochloride; Drug: Omeprazole; Drug: Pioglitazone hydrochloride; Drug: Buproprion; Drug: Tolbutamide

What is being measured

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

Pharmacokinetic profile for bupropion
Pharmacokinetic parameters (Cmax, tmax , AUC) for bupropion when administered without or with DS-1971a
Measured: Days 2-6 of Period 1 and Day 9-13 of Period 2
Pharmacokinetic profile for pioglitazone
Pharmacokinetic parameters (Cmax, tmax , AUC) for pioglitazone when administered without or with DS-1971a
Measured: Days 2-4 of Period 1 and Days 9-11 of Period 2
Pharmacokinetic profile for tolbutamide
Pharmacokinetic parameters (Cmax, tmax , AUC) for tolbutamide when administered without or with DS-1971a
Measured: Days 2-4 of Period 1 and Days 9-11 of Period 2
Pharmacokinetic profile for omeprazole
Pharmacokinetic parameters (Cmax, tmax , AUC) for omeprazole when administered without or with DS-1971a
Measured: Day 2 of Period 1 and Day 9 of Period 2
Pharmacokinetic profile for midazolam
Pharmacokinetic parameters (Cmax, tmax , AUC) for midazolam when administered without or with DS-1971a
Measured: Day 1 of Period 1 and Day 8 of Period 2

Secondary outcomes (3)

Pharmacokinetic profile of DS-1971a
PK parameters (Cmax , Ctrough , Cavg , tmax , AUC) of DS 1971a and its metabolites
Measured: Day 1, 3, 6, 8, 9, and 12
Pharmacokinetic profile of metabolites of substrates
PK parameters (Cmax , tmax , AUC, metabolite/parent ratio) of metabolites of bupropion, omeprazole, tolbutamide, and midazolam
Measured: Days 1-6 of Period 1 and Days 8-13 of Period 2
number and severity of Adverse Events
The number, severity, and percentage of subjects reporting Treatment Emergent Adverse Events (TEAEs) will be tabulated.
Measured: Day 0 - Week 9

Timeline

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

May 2015Jul 2015

First posted16 Jun 2015 (estimated)
Study startMay 2015
Primary completionJul 2015
Study completionJul 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for HealthyStudies of the same condition, open and under way.
More trials run by Daiichi SankyoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02473627
Sponsor's protocol ID: DS1971-A-E105
Status last verified: Nov 2015
First submitted: 12 Jun 2015
Last updated: 5 Nov 2015
Results posted: No
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 5 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A PHASE 1, OPEN-LABEL, CROSS-OVER, FIXED SEQUENCE STUDY TO EVALUATE THE EFFECT OF MULTIPLE DOSES OF DS-1971A ON THE SINGLE DOSE PHARMACOKINETICS OF PROBE SUBSTRATES FOR CYP2B6, CYP2C8, CYP2C9, CYP2C19 AND CYP3A4 ENZYMES IN HEALTHY MALE AND FEMALE SUBJECTS
ClinicalTrials.gov ID: NCT02473627
Acronym / sponsor ID: DS1971-A-E105
Conditions: Healthy
Keywords: Pharmacokinetics
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: Daiichi SankyoIndustry (pharma, biotech, devices)
Study start: May 2015
Primary completion: Jul 2015 (actual)
Study completion: Jul 2015 (actual)
First posted: 16 Jun 2015 (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.

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Period 1	Experimental	Drug: midazolam hydrochloride, Drug: Omeprazole, Drug: Pioglitazone hydrochloride, Drug: Buproprion, Drug: TolbutamidePeriod 1 Day 1: single oral dose of 2.5 mg midazolam hydrochloride Day 2: single oral cocktail dose of 20 mg omeprazole, 15 mg pioglitazone hydrochloride, 500 mg tolbutamide and 150 mg bupropion
Period 2	Experimental	Drug: DS-1971a, Drug: midazolam hydrochloride, Drug: Omeprazole, Drug: Pioglitazone hydrochloride, Drug: Buproprion, Drug: TolbutamidePeriod 2 Days 1 through 12 repeated doses of 400 mg DS-1971a administered orally bid . On the days listed below, each probe substrate(s) will be coadministered with the morning dose of DS 1971a: Day 8: single oral dose of 2.5 mg midazolam hydrochloride Day 9: single oral cocktail dose of 20 mg omeprazole, 15 mg pioglitazone hydrochloride, 500 mg tolbutamide and 150 mg bupropion

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Male or female aged 18 to 65 years, inclusive.
Be in good general health as determined by medical history, physical examination and Screening investigations, and be taking no regular medication.
A body mass index (BMI) in the range 18 to 30 kg/m2, inclusive, and weighing between 50 and 100 kg, inclusive. BMI is calculated as weight [kg]/(height [m])*2.
Female subjects must be of nonchildbearing potential as follows:
Must be postmenopausal (the last menstrual period was at least 12 months before Screening, and a follicle stimulating hormone [FSH] test at Screening confirms postmenopausal status); or Must be surgically sterile having undergone hysterectomy, bilateral oophorectomy, bilateral salpingectomy and/or bilateral tubal ligation.

Key exclusion criteria (21 listed)

Clinically relevant abnormal history, physical findings, ECG findings or laboratory values that could interfere with the objectives of the study or the safety of the subject.
Presence of history of acute or chronic illness, including (but not limited to) liver or kidney disease, hypertension, seizures, or any known impairment of endocrine, or other specific body-organ dysfunction.
Presence or history of severe adverse reaction to any medicine.
Presence or history of malignant disease.
Acute or chronic infectious disease, including human immunodeficiency virus (HIV), hepatitis B virus or C virus (HCV) infection.

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
DS-1971a200mg tablet	Drug	Period 2
midazolam hydrochloride2.5mg oromucosal liquid	Drug	Period 1, Period 2
Omeprazole20mg gastro-resistant capsule	Drug	Period 1, Period 2
Pioglitazone hydrochloride15mg tablet	Drug	Period 1, Period 2
Buproprion150mg Prolonged release tablet	Drug	Period 1, Period 2
Tolbutamide500mg tablet	Drug	Period 1, Period 2

Primary outcome

Pharmacokinetic profile for bupropion
Time frame: Days 2-6 of Period 1 and Day 9-13 of Period 2
Pharmacokinetic parameters (Cmax, tmax , AUC) for bupropion when administered without or with DS-1971a
Pharmacokinetic profile for pioglitazone
Time frame: Days 2-4 of Period 1 and Days 9-11 of Period 2
Pharmacokinetic parameters (Cmax, tmax , AUC) for pioglitazone when administered without or with DS-1971a
Pharmacokinetic profile for tolbutamide
Time frame: Days 2-4 of Period 1 and Days 9-11 of Period 2
Pharmacokinetic parameters (Cmax, tmax , AUC) for tolbutamide when administered without or with DS-1971a
Pharmacokinetic profile for omeprazole
Time frame: Day 2 of Period 1 and Day 9 of Period 2
Pharmacokinetic parameters (Cmax, tmax , AUC) for omeprazole when administered without or with DS-1971a
Pharmacokinetic profile for midazolam
Time frame: Day 1 of Period 1 and Day 8 of Period 2
Pharmacokinetic parameters (Cmax, tmax , AUC) for midazolam when administered without or with DS-1971a

3 secondary outcomes

Pharmacokinetic profile of DS-1971a
Time frame: Day 1, 3, 6, 8, 9, and 12
Pharmacokinetic profile of metabolites of substrates
Time frame: Days 1-6 of Period 1 and Days 8-13 of Period 2
number and severity of Adverse Events
Time frame: Day 0 - Week 9

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 5 Nov 2015.

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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.

The record lists no contact. Use the official record to reach the sponsor.

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 DS-1971a, midazolam hydrochloride and Omeprazole in people with Healthy, run by Daiichi Sankyo 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 9 inclusion and 21 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 5 Nov 2015. 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?

Pharmacokinetic profile for bupropion (time frame: Days 2-6 of Period 1 and Day 9-13 of Period 2). 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 NCT02473627.

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 5 Nov 2015.