Hepatitis CPhase 1NCT01830205

Pharmacokinetic and Safety Study of Daclatasvir in Patients With Renal Impairment

A Phase 1 study testing Daclatasvir in people with Hepatitis C, run by Bristol-Myers Squibb at 2 sites in United States.

Completed

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

Official record

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Trial summary

The purpose of this study is to assess the effect of renal function impairment on the single dose pharmacokinetics of Daclatasvir. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hepatitis C
What is being tested?: Daclatasvir
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 58 participants
Where: 2 sitesUnited States
Study dates: Sep 2012to Jun 2013
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Meet renal function criteria in one of four categories

Who cannot join

Unstable or uncontrolled medical conditions

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Davita Clinical Research
Minneapolis, Minnesota, 55404
Orlando Clinical Research Center
Orlando, Florida, 32809

Other trials in United States

About this study

Official title: Single Dose Pharmacokinetics and Safety of Daclatasvir in Subjects With Renal Function Impairment

The purpose of this study is to assess the effect of renal function impairment on the single dose pharmacokinetics of Daclatasvir.

Read the detailed description

Treatment, Parallel Assignment, Open Label, Non-Randomized, Single Dose Adaptive Design, Pharmacokinetics Study

Conditions: Hepatitis C
Being tested: Daclatasvir
Medical subject headings: Hepatitis C

What participants receive

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

DaclatasvirDrug
Also called BMS-790052

Study groups in NCT01830205
Study group	Role	What they receive
Group A (Normal renal function): Daclatasvir	Experimental	Daclatasvir 60 mg tablet by mouth single dose on Day 1 Receives: Drug: Daclatasvir
Group B (End Stage Renal Disease): Daclatasvir	Experimental	Daclatasvir 60 mg tablet by mouth single dose on Day 1 Receives: Drug: Daclatasvir
Group C (Moderate renal impairment): Daclatasvir	Experimental	Daclatasvir 60 mg tablet by mouth single dose on Day 1 Receives: Drug: Daclatasvir
Group D (Severe renal impairment): Daclatasvir	Experimental	Daclatasvir 60 mg tablet by mouth single dose on Day 1 Receives: Drug: Daclatasvir

What is being measured

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

Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Daclatasvir
AUC(INF) was estimated by summing the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration and the extrapolated area, computed by the quotient of the last observable concentration and elimination rate constant. The pharmacokinetic (PK) analysis was based on Cockcroft-Gault (C-G) creatinine clearance (CLcr) grouping method: normal renal function, end stage renal disease (ESRD), moderate and severe renal impairment. Mild participants were counted as per their original allocation.
Measured: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose

Secondary outcomes (15)

Unbound Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity Time (AUC(INF)u) of Daclatasvir
AUC(INF)u was calculated by multiplying the area under the plasma concentration-time curve from time zero extrapolated to infinite time by mean fraction of unbound drug from 1 hour post-dose time point.
Measured: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of Daclatasvir
Maximum observed plasma concentration following drug administration from the raw plasma concentration-time data. The plasma samples were analyzed for daclatasvir by using a validated liquid chromatography tandem mass spectrometric (LC-MS/MS) assay.
Measured: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Unbound Maximum Observed Plasma Concentrations of Daclatasvir
Unbound Maximum observed plasma concentrations (Cmaxu) was calculated by multiplying maximum observed plasma concentrations by mean fraction of unbound drug from 1 hour post-dose time point.
Measured: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Area Under the Plasma Concentration-time Curve From Time Zero to Last Measurable Concentration [AUC(0-T)] of Daclatasvir
AUC(0-T) was calculated as the sum of linear trapezoids using non-compartmental analysis.
Measured: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Daclatasvir
Tmax was defined as the time required to reach maximum observed plasma concentration. Tmax was directly determined from the raw plasma concentration-time data.
Measured: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Plasma Half-life (T-half) of Daclatasvir
Terminal half-life was the time required for one half of the total amount of administered drug eliminated from the body.
Measured: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Apparent Total Body Clearance (CLT/F) of Daclatasvir
Apparent total body clearance was calculated by dividing the dose by area under the plasma concentration-time curve from time zero extrapolated to infinite time.
Measured: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Unbound Apparent Clearance (CLU/F) of Daclatasvir
The CLU/F was calculated by dividing the apparent total body clearance by mean fraction of unbound drug from 1 hour post dose time point.
Measured: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Percent Urinary Recovery (%UR) of Daclatasvir
The percentage of daclatasvir recovered in the urine was determined by using validated liquid chromatography-tandem mass spectrometry methods. The sum of the percentage of dose recovered in urine from all intervals was calculated to obtain the total percentage of urinary excretion.
Measured: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Renal Clearance (CLR) of Daclatasvir
The CLR was calculated by dividing the total amount excreted in the urine from 0 to 96 hours by the area under the plasma concentration-time curve from time zero extrapolated to infinite time.
Measured: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Apparent Volume of Distribution (Vd/F) of Daclatasvir
The Vd/F was calculated by dividing the product of the dose and mean residence time by area under the plasma concentration-time curve from time zero extrapolated to infinite time.
Measured: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events and Who Died
Adverse event (AE) was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalisation.
Measured: First dose up to Day 5 post last dose for AEs; up to 30 days post last dose for SAEs
Number of Participants With Clinically Significant Laboratory Marked Abnormalities Reported as Adverse Events
Significant laboratory abnormalities were defined as any test results which were observed beyond the clinically acceptable limits as per the discretion of investigator.
Measured: Baseline up to Day 5 post dose
Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Reported as Adverse Events
The number of participants with clinically relevant changes in ECG which were considered as adverse events was determined.
Measured: Baseline up to Day 5 post dose
Number of Participants With Out-of-range Vital Signs Reported as Adverse Events
The total number of participants with abnormal range vital signs which were considered as adverse events was determined.
Measured: Baseline up to Day 5 post dose

Timeline

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

Sep 2012Jun 2013

First posted12 Apr 2013 (estimated)
Study startSep 2012
Primary completionJun 2013
Study completionJun 2013

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 Hepatitis CStudies of the same condition, open and under way.
More trials run by Bristol-Myers SquibbThe 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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 58 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01830205
Sponsor's protocol ID: AI444-063
Status last verified: Nov 2015
First submitted: 10 Apr 2013
Last updated: 16 Nov 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Garimella T, Wang R, Luo WL, Hwang C, Sherman D, Kandoussi H, Marbury TC, Alcorn H, Bertz R, Bifano M. Single-dose pharmacokinetics and safety of daclatasvir in subjects with renal function impairment. Antivir Ther. 2015;20(5):535-43. doi: 10.3851/IMP2941. Epub 2015 Feb 5.
PubMed 25654812

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 16 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Single Dose Pharmacokinetics and Safety of Daclatasvir in Subjects With Renal Function Impairment
ClinicalTrials.gov ID: NCT01830205
Acronym / sponsor ID: AI444-063
Conditions: Hepatitis C
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 58 participants (actual)
Lead sponsor: Bristol-Myers SquibbIndustry (pharma, biotech, devices)
Study start: Sep 2012
Primary completion: Jun 2013 (actual)
Study completion: Jun 2013 (actual)
First posted: 12 Apr 2013 (estimated)
Results: Posted 16 Nov 2015

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 assess the effect of renal function impairment on the single dose pharmacokinetics of Daclatasvir.

Detailed description

Treatment, Parallel Assignment, Open Label, Non-Randomized, Single Dose Adaptive Design, Pharmacokinetics Study

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Group A (Normal renal function): Daclatasvir	Experimental	Drug: DaclatasvirDaclatasvir 60 mg tablet by mouth single dose on Day 1
Group B (End Stage Renal Disease): Daclatasvir	Experimental	Drug: DaclatasvirDaclatasvir 60 mg tablet by mouth single dose on Day 1
Group C (Moderate renal impairment): Daclatasvir	Experimental	Drug: DaclatasvirDaclatasvir 60 mg tablet by mouth single dose on Day 1
Group D (Severe renal impairment): Daclatasvir	Experimental	Drug: DaclatasvirDaclatasvir 60 mg tablet by mouth single dose on Day 1

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

Meet renal function criteria in one of four categories

Key exclusion criteria (1 listed)

Unstable or uncontrolled medical conditions

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
DaclatasvirAlso: BMS-790052	Drug	Group A (Normal renal function): Daclatasvir, Group B (End Stage Renal Disease): Daclatasvir, Group C (Moderate renal impairment): Daclatasvir, Group D (Severe renal impairment): Daclatasvir

Primary outcome

Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Daclatasvir
Time frame: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
AUC(INF) was estimated by summing the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration and the extrapolated area, computed by the quotient of the last observable concentration and elimination rate constant. The pharmacokinetic (PK) analysis was based on Cockcroft-Gault (C-G) creatinine clearance (CLcr) grouping method: normal renal function, end stage renal disease (ESRD), moderate and severe renal impairment. Mild participants were counted as per their original allocation.

15 secondary outcomes

Unbound Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity Time (AUC(INF)u) of Daclatasvir
Time frame: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of Daclatasvir
Time frame: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Unbound Maximum Observed Plasma Concentrations of Daclatasvir
Time frame: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Area Under the Plasma Concentration-time Curve From Time Zero to Last Measurable Concentration [AUC(0-T)] of Daclatasvir
Time frame: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Daclatasvir
Time frame: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Plasma Half-life (T-half) of Daclatasvir
Time frame: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Apparent Total Body Clearance (CLT/F) of Daclatasvir
Time frame: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Unbound Apparent Clearance (CLU/F) of Daclatasvir
Time frame: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Percent Urinary Recovery (%UR) of Daclatasvir
Time frame: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Renal Clearance (CLR) of Daclatasvir
Time frame: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Apparent Volume of Distribution (Vd/F) of Daclatasvir
Time frame: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events and Who Died
Time frame: First dose up to Day 5 post last dose for AEs; up to 30 days post last dose for SAEs
Number of Participants With Clinically Significant Laboratory Marked Abnormalities Reported as Adverse Events
Time frame: Baseline up to Day 5 post dose
Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Reported as Adverse Events
Time frame: Baseline up to Day 5 post dose
Number of Participants With Out-of-range Vital Signs Reported as Adverse Events
Time frame: Baseline up to Day 5 post dose

Results and safety

Results posted to the registry on 16 Nov 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Normal Renal Function/Mild Renal Impairment	12	12
Mild/Moderate Renal Impairment	6	6
Mild/Severe Renal Impairment	6	6
End Stage Renal Disease	12	12

Primary outcome: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Daclatasvir

Time frame: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: nanograms*hours/milliliter (ng*h/mL)

Measure	Normal Renal Function n = 11	Mild Renal Impairment n = 4	Moderate Renal Impairment n = 5	Severe Renal Impairment n = 6	End Stage Renal Disease n = 10
Value	11215.264 (40)	21261.199 (62)	24789.951 (35)	21946.450 (39)	14257.489 (25)

Population analysed: PK data set included all participants who received at least 1 dose of daclatasvir with adequate PK profiles. The PK analysis was based on the C-G CLcr grouping method: normal renal function (n=11), ESRD (n=10), moderate (n=5) and severe renal impairment (n=6). Mild participants (n=4) are also counted as per their original allocation.

15 secondary outcomes are reported in the full results.

Adverse events

Time frame: First dose up to Day 5 post last dose of study treatment for AEs; up to 30 days post last dose for SAEs. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group-A	0 of 12 (0%)	0 of 12 (0%)	Not reported
Mild/Moderate Renal Impairment	0 of 6 (0%)	1 of 6 (16.7%)	Not reported
Mild/Severe Renal Impairment	0 of 6 (0%)	1 of 6 (16.7%)	Not reported
End Stage Renal Disease	0 of 12 (0%)	3 of 12 (25%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 25654812Garimella T, Wang R, Luo WL, Hwang C, Sherman D, Kandoussi H, Marbury TC, Alcorn H, Bertz R, Bifano M. Single-dose pharmacokinetics and safety of daclatasvir in subjects with renal function impairment. Antivir Ther. 2015;20(5):535-43. doi: 10.3851/IMP2941. Epub 2015 Feb 5.

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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.

Bristol-Myers Squibb study director

Bristol-Myers Squibb

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Daclatasvir in people with Hepatitis C, run by Bristol-Myers Squibb at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 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 16 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 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Nov 2015). 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?

Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Daclatasvir (time frame: Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose). 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 NCT01830205, 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 16 Nov 2015.