Trial Outcomes & Findings for A Phase IIb Study to Evaluate the Safety of Zibotentan/Dapagliflozin in Participants With Cirrhosis-ZEAL-UNLOCK (NCT NCT06269484)

NCT ID: NCT06269484

Last Updated: 2026-01-20

Results Overview

Cumulative number of subjects with event of composite fluid retention endpoint

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 73 participants
• Primary outcome timeframe: baseline to Week 6
• Results posted on: 2026-01-20

Participant Flow

The first participant was enrolled on February 2024 and the last participant was enrolled in September 2024.

Of 88 study participants, 73 met inclusion criteria and were not withdrawn by subject and subsequently randomised to treatment.

Participant milestones

Measure	Zibo/Dapa Zibotentan capsule + dapagliflozin 10 mg	Zibo Zibotentan capsule + placebo	Placebo Placebo + placebo
Overall Study STARTED	24	25	24
Overall Study TREATED	24	24	24
Overall Study COMPLETED	20	24	22
Overall Study NOT COMPLETED	4	1	2

Reasons for withdrawal

Measure	Zibo/Dapa Zibotentan capsule + dapagliflozin 10 mg	Zibo Zibotentan capsule + placebo	Placebo Placebo + placebo
Overall Study Withdrawal by Subject	3	0	2
Overall Study All other reasons apart from specified	1	0	0
Overall Study Randomised but not started treatment	0	1	0

Baseline Characteristics

A Phase IIb Study to Evaluate the Safety of Zibotentan/Dapagliflozin in Participants With Cirrhosis-ZEAL-UNLOCK

Baseline characteristics by cohort

Measure	Zibo/Dapa n=24 Participants Zibotentan capsule + dapagliflozin 10 mg	Zibo n=24 Participants Zibotentan capsule + placebo	Placebo n=24 Participants Placebo + placebo	Total n=72 Participants Total of all reporting groups
Age, Continuous	60.2 Years STANDARD_DEVIATION 11.4 • n=37 Participants	59.5 Years STANDARD_DEVIATION 8.9 • n=44 Participants	62.6 Years STANDARD_DEVIATION 8.4 • n=40 Participants	60.8 Years STANDARD_DEVIATION 9.6 • n=121 Participants
Sex: Female, Male Female	6 Participants n=37 Participants	8 Participants n=44 Participants	7 Participants n=40 Participants	21 Participants n=121 Participants
Sex: Female, Male Male	18 Participants n=37 Participants	16 Participants n=44 Participants	17 Participants n=40 Participants	51 Participants n=121 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=37 Participants	3 Participants n=44 Participants	1 Participants n=40 Participants	8 Participants n=121 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=37 Participants	21 Participants n=44 Participants	23 Participants n=40 Participants	64 Participants n=121 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=37 Participants	0 Participants n=44 Participants	0 Participants n=40 Participants	0 Participants n=121 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=37 Participants	0 Participants n=44 Participants	0 Participants n=40 Participants	0 Participants n=121 Participants
Race (NIH/OMB) Asian	4 Participants n=37 Participants	4 Participants n=44 Participants	4 Participants n=40 Participants	12 Participants n=121 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=37 Participants	0 Participants n=44 Participants	0 Participants n=40 Participants	0 Participants n=121 Participants
Race (NIH/OMB) Black or African American	0 Participants n=37 Participants	0 Participants n=44 Participants	0 Participants n=40 Participants	0 Participants n=121 Participants
Race (NIH/OMB) White	20 Participants n=37 Participants	20 Participants n=44 Participants	20 Participants n=40 Participants	60 Participants n=121 Participants
Race (NIH/OMB) More than one race	0 Participants n=37 Participants	0 Participants n=44 Participants	0 Participants n=40 Participants	0 Participants n=121 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=37 Participants	0 Participants n=44 Participants	0 Participants n=40 Participants	0 Participants n=121 Participants

PRIMARY outcome

Timeframe: baseline to Week 6

Population: All randomised subjects who received at least one dose of treatment are included in the analysis. For intercurrent events treatment policy strategy was used. No imputation was performed.

Cumulative number of subjects with event of composite fluid retention endpoint

Outcome measures

Measure	Zibo/Dapa n=24 Participants Zibotentan capsule + dapagliflozin 10 mg	Zibo n=24 Participants Zibotentan capsule + placebo	Placebo n=24 Participants Placebo + placebo
Cumulative Number of Subjects With Any of the Components of the Composite Endpoint: >2kg Increase in Body Weight (Office-based), >2 L Increase in Total Body Water, Increase in 2 or More Loop-diuretic Equivalents, Fluid Retention Adverse Event (AE)	14 Participants	14 Participants	6 Participants

SECONDARY outcome

Timeframe: at Week 6

Population: All randomised subjects who received at least one dose of treatment are included in the analysis. For intercurrent events treatment policy strategy was used. No imputation was performed.

Change in site body weight

Outcome measures

Measure	Zibo/Dapa n=20 Participants Zibotentan capsule + dapagliflozin 10 mg	Zibo n=24 Participants Zibotentan capsule + placebo	Placebo n=22 Participants Placebo + placebo
Change From Baseline in Body Weight	-1.08 kg Interval -1.88 to -0.28	0.64 kg Interval -0.11 to 1.39	-0.53 kg Interval -1.31 to 0.24

SECONDARY outcome

Timeframe: at Week 6

Population: All randomised subjects who received at least one dose of treatment are included in the analysis. For intercurrent events treatment policy strategy was used. No imputation was performed.

Outcome measures

Measure	Zibo/Dapa n=20 Participants Zibotentan capsule + dapagliflozin 10 mg	Zibo n=24 Participants Zibotentan capsule + placebo	Placebo n=22 Participants Placebo + placebo
Change From Baseline in Body Fat Mass	-1.68 kg Interval -2.43 to -0.94	-0.23 kg Interval -0.93 to 0.48	-0.30 kg Interval -1.03 to 0.42

SECONDARY outcome

Timeframe: at Week 6

Population: All randomised subjects who received at least one dose of treatment are included in the analysis. For intercurrent events treatment policy strategy was used. No imputation was performed.

Outcome measures

Measure	Zibo/Dapa n=20 Participants Zibotentan capsule + dapagliflozin 10 mg	Zibo n=24 Participants Zibotentan capsule + placebo	Placebo n=22 Participants Placebo + placebo
Change From Baseline in Total Body Water	0.36 L Interval -0.22 to 0.94	0.66 L Interval 0.12 to 1.21	-0.36 L Interval -0.92 to 0.21

SECONDARY outcome

Timeframe: at Week 6

Population: All randomised subjects who received at least one dose of treatment are included in the analysis. For intercurrent events treatment policy strategy was used. No imputation was performed.

Outcome measures

Measure	Zibo/Dapa n=20 Participants Zibotentan capsule + dapagliflozin 10 mg	Zibo n=24 Participants Zibotentan capsule + placebo	Placebo n=22 Participants Placebo + placebo
Change From Baseline in Extracellular Water Volume	0.38 L Interval 0.09 to 0.66	0.38 L Interval 0.11 to 0.65	-0.15 L Interval -0.43 to 0.13

SECONDARY outcome

Timeframe: at Week 6

Population: All randomised subjects who received at least one dose of treatment are included in the analysis. For intercurrent events treatment policy strategy was used. No imputation was performed.

Outcome measures

Measure	Zibo/Dapa n=20 Participants Zibotentan capsule + dapagliflozin 10 mg	Zibo n=24 Participants Zibotentan capsule + placebo	Placebo n=22 Participants Placebo + placebo
Change From Baseline in Intracellular Water Volume	0.08 L Interval -0.24 to 0.4	0.30 L Interval 0.0 to 0.6	-0.19 L Interval -0.5 to 0.12

SECONDARY outcome

Timeframe: at Week 6

Population: All randomised subjects who received at least one dose of treatment are included in the analysis. For intercurrent events treatment policy strategy was used. No imputation was performed.

Change in home body weight

Outcome measures

Measure	Zibo/Dapa n=16 Participants Zibotentan capsule + dapagliflozin 10 mg	Zibo n=20 Participants Zibotentan capsule + placebo	Placebo n=15 Participants Placebo + placebo
Change in Body Weight (kg) Over Time Course of Study	-1.754 kg Interval -2.541 to -0.967	0.021 kg Interval -0.692 to 0.734	-1.256 kg Interval -2.077 to -0.435

SECONDARY outcome

Timeframe: at Week 6

Population: All randomised subjects who received at least one dose of treatment are included in the analysis. For intercurrent events treatment policy strategy was used. No imputation was performed.

One loop-diuretic equivalent = 40 mg furosemide = 1 mg bumetanide = 20 mg torsemide = 50 mg ethacrynic acid. In Japan, one loop-diuretic equivalent = 40 mg furosemide = 8 mg torsemide = 60 mg azosemide.

Outcome measures

Measure	Zibo/Dapa n=20 Participants Zibotentan capsule + dapagliflozin 10 mg	Zibo n=24 Participants Zibotentan capsule + placebo	Placebo n=22 Participants Placebo + placebo
Change in Total Dosage of Loop-diuretic Equivalents Use	1.282 Loop-diuretic *mg* equivalent Interval -2.045 to 4.609	6.340 Loop-diuretic *mg* equivalent Interval 3.104 to 9.576	1.338 Loop-diuretic *mg* equivalent Interval -1.953 to 4.629

SECONDARY outcome

Timeframe: from baseline to Week 6

Population: All randomised subjects who received at least one dose of treatment are included in the analysis. For intercurrent events treatment policy strategy was used. No imputation was performed.

Cumulative number of subjects with event of composite and the components of total body water and total dosage of loop-diuretic equivalents

Outcome measures

Measure	Zibo/Dapa n=24 Participants Zibotentan capsule + dapagliflozin 10 mg	Zibo n=24 Participants Zibotentan capsule + placebo	Placebo n=24 Participants Placebo + placebo
Cumulative Number of Subjects With Either of the Two Components of This Composite: 1. >3 L Increase in Total Body Water Volume From Baseline to Week 6 2. Increase in 3 or More Loop-diuretics Equivalents Use	7 Participants	9 Participants	2 Participants

SECONDARY outcome

Timeframe: at Week 6

Population: All randomised subjects who received at least one dose of treatment are included in the analysis. For intercurrent events treatment policy strategy was used. No imputation was performed.

Outcome measures

Measure	Zibo/Dapa n=21 Participants Zibotentan capsule + dapagliflozin 10 mg	Zibo n=24 Participants Zibotentan capsule + placebo	Placebo n=22 Participants Placebo + placebo
Absolute Change in Systolic Blood Pressure	-12.0 mmHg Interval -16.1 to -7.9	-2.6 mmHg Interval -6.5 to 1.2	-0.1 mmHg Interval -4.1 to 3.9

SECONDARY outcome

Timeframe: at Week 6

Population: All randomised subjects who received at least one dose of treatment are included in the analysis. For intercurrent events treatment policy strategy was used. No imputation was performed.

Outcome measures

Measure	Zibo/Dapa n=21 Participants Zibotentan capsule + dapagliflozin 10 mg	Zibo n=24 Participants Zibotentan capsule + placebo	Placebo n=22 Participants Placebo + placebo
Absolute Change in Diastolic Blood Pressure	-9.1 mmHg Interval -11.3 to -6.8	-2.5 mmHg Interval -4.7 to -0.3	1.8 mmHg Interval -0.5 to 4.0

Adverse Events

Zibo/Dapa

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Zibo

Serious events: 2 serious events

Other events: 15 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Zibo/Dapa n=24 participants at risk Zibotentan capsule + dapagliflozin 10 mg	Zibo n=24 participants at risk Zibotentan capsule + placebo	Placebo n=24 participants at risk Placebo + placebo
Gastrointestinal disorders Ascites	0.00% 0/24 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	0.00% 0/24 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	4.2% 1/24 • Number of events 1 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/24 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	8.3% 2/24 • Number of events 2 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	0.00% 0/24 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.
Gastrointestinal disorders Oesophageal varices haemorrhage	4.2% 1/24 • Number of events 1 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	0.00% 0/24 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	0.00% 0/24 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.

Other adverse events

Measure	Zibo/Dapa n=24 participants at risk Zibotentan capsule + dapagliflozin 10 mg	Zibo n=24 participants at risk Zibotentan capsule + placebo	Placebo n=24 participants at risk Placebo + placebo
Blood and lymphatic system disorders Thrombocytopenia	8.3% 2/24 • Number of events 2 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	0.00% 0/24 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	0.00% 0/24 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.
Metabolism and nutrition disorders Fluid retention	12.5% 3/24 • Number of events 3 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	4.2% 1/24 • Number of events 1 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	0.00% 0/24 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.
Nervous system disorders Headache	20.8% 5/24 • Number of events 5 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	25.0% 6/24 • Number of events 7 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	4.2% 1/24 • Number of events 1 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.
Vascular disorders Orthostatic hypotension	12.5% 3/24 • Number of events 5 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	8.3% 2/24 • Number of events 2 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	0.00% 0/24 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.3% 2/24 • Number of events 2 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	12.5% 3/24 • Number of events 3 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	0.00% 0/24 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.
Gastrointestinal disorders Ascites	4.2% 1/24 • Number of events 1 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	12.5% 3/24 • Number of events 3 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	0.00% 0/24 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.
Gastrointestinal disorders Constipation	8.3% 2/24 • Number of events 2 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	4.2% 1/24 • Number of events 1 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	0.00% 0/24 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.
Gastrointestinal disorders Dry mouth	8.3% 2/24 • Number of events 2 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	0.00% 0/24 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	0.00% 0/24 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.
General disorders Oedema peripheral	8.3% 2/24 • Number of events 2 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	20.8% 5/24 • Number of events 7 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	4.2% 1/24 • Number of events 1 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.
Investigations Weight increased	8.3% 2/24 • Number of events 3 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	12.5% 3/24 • Number of events 8 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.	8.3% 2/24 • Number of events 2 • Adverse events reported are adverse events with an onset date on or after the date of first dose of IP and until end of study for each participant which in general was 6 weeks treatment period and 2 weeks follow-up period.

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding study results for a period that is less than or equal to 60 days from the date that the communication is submitted to the sponsor for review. The sponsor can require changes to the communication but cannot unilaterally extend the embargo.
• Publication restrictions are in place

Restriction type: OTHER