Trial Outcomes & Findings for A Phase IIIb Study to Compare Entecavir Plus Tenofovir vs. Adefovir Added to Continuing Lamivudine Therapy in Adult Patients With Lamivudine-Resistant Hepatitis B Infection (NCT NCT00605384)

Results Overview

using the Roche COBAS® TaqMan HBV Test for use with the High Pure System (HPS) assay, by Polymerase Chain Reaction (PCR); HBV DNA \< 50 IU/mL = approximately 300 copies/mL

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

4 participants

Primary outcome timeframe

Week 48

Results posted on

2010-11-23

Participant Flow

A total of 84 subjects were to be treated with entecavir (ETV) plus tenofovir (TNF) or adefovir (ADV) added to continuing lamivudine (LVD).

Of the 4 subjects enrolled, 2 were not randomized (reasons: "Subject no longer meets study criteria" and "Other"). Both subjects randomized were treated as well.

Participant milestones

Participant milestones
Measure	Entecavir + Tenofovir Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks	Adefovir + Continuing Lamivudine Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
Overall Study STARTED	1	1
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase IIIb Study to Compare Entecavir Plus Tenofovir vs. Adefovir Added to Continuing Lamivudine Therapy in Adult Patients With Lamivudine-Resistant Hepatitis B Infection

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Entecavir + Tenofovir n=1 Participants Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks	Adefovir + Continuing Lamivudine n=1 Participants Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks	Total n=2 Participants Total of all reporting groups
Age, Customized Between 18 and 65 years	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Age, Customized >=65 years	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 48

Population: Due to early study termination, none of the efficacy endpoints were analyzed.

using the Roche COBAS® TaqMan HBV Test for use with the High Pure System (HPS) assay, by Polymerase Chain Reaction (PCR); HBV DNA \< 50 IU/mL = approximately 300 copies/mL

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 96

Population: Due to early study termination, none of the efficacy endpoints were analyzed.

by PCR, using the Roche COBAS®TaqMan - HPS assay; HBV DNA \< 50 IU/mL = approximately 300 copies/mL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 through end of treatment (Week 100 +/- 5 days)

Population: All treated participants. Timeframe for Outcome Measure revised due to study termination. (Study Completion Date=February 2009).

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and/or is an important medical event.

Outcome measures

Outcome measures
Measure	Entecavir + Tenofovir n=1 Participants Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks	Adefovir + Continuing Lamivudine n=1 Participants Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs or Laboratory Abnormalities AEs	1 participants	1 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs or Laboratory Abnormalities SAEs	0 participants	0 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs or Laboratory Abnormalities Deaths	0 participants	0 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs or Laboratory Abnormalities Discontinuations due to AEs	0 participants	0 participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs or Laboratory Abnormalities Discontinuations due to Laboratory Abnormalities	0 participants	0 participants

SECONDARY outcome

Timeframe: Week 48, Week 96

Population: Due to early study termination, none of the efficacy endpoints were analyzed.

by PCR, using the Roche for the Roche COBAS® TaqMan - HPS assay. LLD = 4.8 IU/mL (approximately 28 copies/mL)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 48, Week 96

Population: Due to early study termination, none of the efficacy endpoints were analyzed.

Number of Participants with HBV DNA \<LLD (4.8); LLD to \<50; 50 to \<172; 172 to \<1,720; 1,720 to \<17,200; and ≥17,200 IU/mL (\<LLD (28); 28 to \<300; 300 to \<1,000; 1,000 to \<10,000; 10,000 to \<100,000; and ≥100,000 copies/mL by PCR, using the Roche COBAS®TaqMan - HPS assay

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 48, Week 96

Population: Due to early study termination, none of the efficacy endpoints was analyzed.

by PCR, using the Roche COBAS®TaqMan - HPS assay

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 48, Week 96

Population: Due to early study termination, none of the efficacy endpoints were analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 48, Week 96

Population: Due to early study termination, none of the efficacy endpoints was analyzed.

HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 48, Week 96

Population: Due to early study termination, none of the efficacy endpoints were analyzed.

HBe seroconversion = HBeAg loss and presence of hepatitis B e-antibody (HBeAb)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 48, Week 96

Population: Due to early study termination, none of the efficacy endpoints were analyzed.

Hepatitis B surface antigen (HBsAg) = a part of the hepatitis B virus that, when in the blood, is an early marker of infection

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 48, Week 96

Population: Due to early study termination, none of the efficacy endpoints were analyzed.

Hepatitis B surface antigen (HBsAg) = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBsAb = HBsAg antibodies. HBs Seroconversion = HBsAg loss and presence of HBseAb

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 48, Week 96

Population: Due to early study termination, none of the efficacy endpoints were analyzed.

HBV DNA ≥ 50 IU/mL = approximately 300 copies/mL

Outcome measures

Outcome data not reported

Adverse Events

Entecavir + Tenofovir

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Adefovir + Continuing Lamivudine

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Entecavir + Tenofovir n=1 participants at risk Tablets, Oral, Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks	Adefovir + Continuing Lamivudine n=1 participants at risk Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
Gastrointestinal disorders Hyperchlorhydria	100.0% 1/1	0.00% 0/1
Hepatobiliary disorders Hepatitis	0.00% 0/1	100.0% 1/1
General disorders Fatigue	0.00% 0/1	100.0% 1/1

Additional Information

BMS Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER