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ZD4054

Phase 3

Prostate Cancer | Small molecule | Oncology |AstraZeneca PLC|Last Updated: Feb 8, 2016

Success Probability

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMC
Total Trials4
Total Enrollment2,881

FDA Designations

No designations recorded

Clinical trial landscape

ZD4054 · 12 trials · 9 indications

Phase 3 2Phase 2 3Phase 1 7
NCT00617669A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) and Docetaxel in Metastatic Hormone Resistant Prostate CancerProstate Cancer
COMPLETED1,494 Analytics
NCT00554229A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) in Hormone Resistant Prostate Cancer With Bone MetastasesProstate Cancer
COMPLETED896 Analytics
PHASE3COMPLETED
A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) and Docetaxel in Metastatic Hormone Resistant Prostate Cancer
Prostate CancerUnlock trial analytics
PHASE3COMPLETED
A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) in Hormone Resistant Prostate Cancer With Bone Metastases
Prostate CancerUnlock trial analytics

Study Endpoints

Primary Endpoints

Overall Survival
Patients were followed for survival up to 40 months

Median time (in months) from randomisation until death using the Kaplan-Meier method.

Time to Death
Patients were followed up for survival every week for the first 3 weeks then every 3 weeks whilst on study medication until the data cut-off (17th January 2010).

Median time (in days) from randomisation until death using the Kaplan-Meier method (Calculator for survival probability)

Time to Progression (TTP)
Follow-up for progression/death was 4-weekly for 2 years after first dose and 3-monthly thereafter. 'Final analysis' results are given - the most recent formal analysis (data cut-off 18th December 2008).

Median time (in days) from randomisation until disease progression, where progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline or death using the Kaplan-Meier method.

Dose Limiting Toxicities (DLTs)
Baseline to Day 29.

DLT is defined as experiencing Common Toxicity Criteria (CTC) grade 3 or 4 headache with onset within 24 h of receiving ZD4054, CTC grade 2 rhinitis leading to the withdrawal of the subject, or other CTC grade 3 or 4 toxicity that was considered to be related to ZD4054 treatment. The numbers of patients with a DLT are reported.

To assess the pharmacokinetics of single and multiple doses of 10mg ZD4054 (Zibotentan) in male, elderly Chinese patients with advanced solid malignancies
PK samples will be taken until Day 16
PK variables
Frequent sampling occasions during study
to assess the maximum of the mean changes in time-matched QTcX (study specific correction) intervals after ZD4054 (Zibotentan) administration (10mg and 30mg) compared to placebo
Pre-dose, 0.5hr, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h
characterise and compare the plasma concentration-time profiles for ZD4054 (Zibotentan) when administered as reference oral solution formulation and as 5 solid oral formulations.
00.50mins, 01.00, 01.15, 01.30, 01.45, 02.00, 02.30, 03.00, 04.00, 06.00, 08.00, 12.00, 24.00, 36.00, 48.00, 72.00, 96.00hrs
Characterise the pharmacokinetic profile of ZD4054 (Zibotentan) following a single 10 mg oral dose in subjects with normal hepatic function and in subjects with varying degrees of hepatic impairment.
predose and 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post-dose
Part A: Maximum Tolerated Dose (MTD)
Part A: Cycle 1 ('Primary analysis' corresponding to data cut-off 5th March 2008)

Secondary Endpoints

Progression Free Survival
Patients were followed for progression up to 40 months
Incidence of Skeletal Related Events
While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)
Time to Prostate-specific Antigen (PSA) Progression
While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)
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Study Design & Arms

AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Placebo + DocetaxelACTIVE_COMPARATORplacebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks
ZD4054 + DocetaxelEXPERIMENTALZD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks
ZD4054EXPERIMENTALZD4054 10 mg oral tablet once daily
PlaceboPLACEBO_COMPARATORMatching Placebo, oral tablets once daily
1EXPERIMENTALZD4054 + Pemetrexed
2PLACEBO_COMPARATORZD4054 matched placebo + pemetrexed
ZD4054 10 mgEXPERIMENTALZD4054 10 mg oral tablet once daily, with best supportive care
ZD4054 15 mgEXPERIMENTALZD4054 15 mg oral tablet once daily, with best supportive care
ZD4054 22.5 mgEXPERIMENTAL2 x 10 mg + 1 x 2.5 mg oral tablets once daily
3EXPERIMENTALZD4054 + ZD4054 placebo + Moxifloxacin placebo
4PLACEBO_COMPARATORZD4054 Placebo + Moxifloxacin placebo
Part AEXPERIMENTALPart A (dose-finding): ZD4054 (Zibotentan) 10 mg oral tablet once daily, with docetaxel 75mg/m\^2 intravenous infusion once per cycle
Part A (ZD4054 (Zibotentan) 15 mg + docetaxel)EXPERIMENTALPart A (dose-finding): ZD4054 (Zibotentan) 15 mg oral tablet once daily, with docetaxel 75mg/m\^2 intravenous infusion once per cycle
Part BEXPERIMENTALPart B (randomised, placebo-controlled): ZD4054 (Zibotentan) Maximum Tolerated Dose (MTD), 15mg, oral tablet once daily, with docetaxel 75mg/m\^2 intravenous infusion once per cycle
Part B (placebo)EXPERIMENTALPart B (randomised, placebo-controlled): Matching placebo oral tablet once daily, with docetaxel 75mg/m\^2 intravenous infusion once per cycle

Interventions

NameTypeDescription
DocetaxelDRUGintravenous infusion given every three weeks
ZD4054DRUG10 mg oral once daily dose
PlaceboDRUGplacebo oral tablet once daily
PemetrexedDRUG500mg2/m IV infusion
ZD4054 15 mgDRUG15 mg oral tablet once daily
ZD4054 10 mgDRUG10mg oral tablet once daily
ZD4054 22.5 mgDRUG2 x 10 mg + 2 x 2.5 mg oral tablets once daily
ZD4054 (Zibotentan)DRUG10 mg ZD4054 (Zibotentan) once daily on Day1, Day4 to Day15
midazolamDRUG -
MoxifloxacinDRUG400 mg capsule
ZD4054 PlaceboDRUG3 tablets
Moxifloxacin placeboDRUG1 capsule
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Eligibility Criteria

Age Range18 Years to N/A
SexMALE
Healthy VolunteersNo
Study Sites147

Inclusion Criteria: Patients who answer TRUE to the following criteria may be eligible to participate in this trial. * Confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate) that has spread to the bone (bone metastasis) * Increasing Prostate Specific Antigen (PSA), collected withi...

Countries:United StatesArgentinaAustraliaBrazilCanadaCzechiaFinlandFranceGermanyHungaryIndiaItalyNetherlandsPeruPolandPortugalRomaniaRussiaSerbiaSouth AfricaSouth KoreaSpainSwedenSwitzerlandTaiwanUnited KingdomAustriaBelgiumChinaDenmarkHong KongJapanMexicoSingaporeBulgariaUkraineIndonesiaNorway
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Competitive Landscape -Prostate Cancer 254 trials

Frequently asked questions about ZD4054

What is ZD4054 used for?

ZD4054, also known as zibotentan, is an investigational small molecule being studied in oncology. Clinical trials have evaluated it in healthy volunteers and in patients with prostate cancer, advanced solid malignancies, and non-small cell lung cancer. It is not approved and remains in clinical development.

Who makes ZD4054?

ZD4054 is being developed by AstraZeneca PLC, which trades under the ticker AZN. The company has sponsored clinical trials of this investigational small molecule in oncology indications.

What phase is ZD4054 in?

ZD4054 is in Phase 1 clinical development. All four completed trials were Phase 1 studies, primarily in healthy volunteers. The drug is investigational and has not been approved by regulatory authorities.

What clinical trials is ZD4054 in?

ZD4054 has completed four Phase 1 trials: NCT00709553, a drug interaction study in healthy subjects in Germany; NCT00710047, a food effect study in the UK; NCT00713336, a QTc interval study in the UK; and NCT00713791, a relative bioavailability study in the US.

Is ZD4054 the same as zibotentan?

Yes, ZD4054 is also known as zibotentan. Clinical trial records use both names interchangeably, with titles such as 'Drug Interaction Study to Assess Multiple Doses of ZD4054 (Zibotentan)'.