Study is Designed to Assess the Safety and Tolerability of AZD4547 at Increasing Doses in Patients With Advanced Tumours
Sponsor
AstraZeneca (Industry)
Overall Status
Terminated
CT.gov ID
NCT00979134
Collaborator
(none)
95
29
3
64.4
3.3
0.1
Study Details
Study Description
Brief Summary
This study is primarily designed to assess the safety and tolerability of AZD4547 at increasing doses in patients with advanced solid malignancies and for whom no standard medication options are available. It also assesses the blood levels and action of AZD4547 in the body over a period of time.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
95 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD4547 in Patients With Advanced Solid Malignancies
Actual Study Start Date
:
Oct 21, 2009
Actual Primary Completion Date
:
Feb 12, 2014
Actual Study Completion Date
:
Mar 5, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part A Ascending doses of AZD4547 administered orally to patients to define the maximum tolerated dose (MTD) and/or a continuous, tolerable Recommended Dose (RD) |
Drug: AZD4547
Single dose is followed by washout 5-10 days before multiple dose
|
| Experimental: Part B Dose expansion phase, at the RD defined in Part A |
Drug: AZD4547
Single dose is followed by washout 5-10 days before multiple dose, and at dose of 80mg twice daily
|
| Experimental: Part C Expansion phase in patients with FGFR1 and FGFR2 amplified tumours commencing at the RD defined from Part A |
Drug: AZD4547
Patients start at a dose of 80 mg twice daily, with no washout
|
Outcome Measures
Primary Outcome Measures
- Number of Patients Who Experienced at Least 1 AE [AEs are monitored from screenng through to 30 day follow up period]
To investigate the safety and tolerability of AZD4547. System organ class (SOC), preferred term (PT), duration and severity all recorded.
- Number of Participants Who Experienced at Least 1 Causally Related AE. [AEs are continually assessed from screening up to 30 day FU period]
To investigate the safety and tolerability of AZD4547. A causally related AE is an AE deemed to be causally related to AZD4547.
- Number of Participants With at Least 1 AE of CTCAE >=G3 [Ongoing up to discontinuation up to 30 day FU.]
To investigate the safety and tolerability of AZD4547
- Number of Participants With at Least 1 Causally Related AE of CTCAE >=G3 [Ongoing up to discontinuation up to 30 day FU.]
To investigate the safety and tolerability of AZD4547
- Number of Participants Who Experienced at Least One SAE [Serious Adverse Events (SAEs) are continually assessed from Screening up to the end of the 30 day FU period.]
To investigate the safety and tolerability of AZD4547. A SAE (Serious Adverse Event) is and AE (adverse Event) which fulfills one of the following criteria that the PI assesses closely such as results in death, immediately life-threatening, requires hospitalisation or prolongation of, results in significant disability, results in birth defect, may jepardise the patient or require intervention to prevent any of the previous outcomes.
- Number of Participants With at Least 1 Causally Related SAE [SAEs are continually monitored from screening to end of 30 FU period]
To investigate the safety and tolerability of AZD4547: SAEs are assessed and deemed as causally related or not to AZD4547
Secondary Outcome Measures
- AUC(0-infinity) [PK samples out to 96 hours "0 to 96 hours post-dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing.]
To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally.
- Tumour Response (Best Objective Response) - Number of Patients With a Confirmed Response of Partial Response (PR) or Confirmed Response (CR) [Baseline assessment, then assessment every 6 weeks after start of treatment until objective disease progression.]
To obtain a preliminary assessment of the anti tumour activity of AZD4547 by evaluation of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1. Objective response = CR + PR; CR=disappearance of all target lesions and PR is >=30% reduction in sum of longest diameter of target lesions
- Cmax (ng/mL) [PK samples out to 96 hours "0-96 hours post dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing.]
To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally.
- Css,Max (ng/mL) [PK samples out to 96 hours "0-96 hours post-dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing.]
To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally.
- AUC,ss(0-infinity) [PK samples out to 96 hours "0-96 hours post dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing.]
To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally.
Eligibility Criteria
Criteria
Ages Eligible for Study:
25 Years
to 149 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Minimum life expectancy of 12 weeks
-
The presence of a solid, malignant tumour that is resistance to standard therapies or for which no standard therapies exist
-
In the expansion for the study patients must have a tumour at least 1cm in size that can be measure using a CT or MRI scan, and provide a tumour sample to the sponsor company for testing of FGFR1 and/or 2 amplification
-
Expansion, 5 groups of advanced cancer
-
Solid tumours,FGFR1 and/or FGFR2 gene amplified
-
Squamous NSCLC, FGFR1 gene low & high amplified
-
Gastric adenocarcinoma, including the lower oesophagus/gastro-oesophageal junction, FGFR2 gene low & high amplified
-
Aged at least 25 years
Exclusion Criteria:
-
Treatment with any other chemotherapy, immunotherapy or anticancer agents within 3 weeks before the first dose of study
-
An inability to be able to take the study medication
-
A bad reaction to AZD4547 or any drugs similar to it in structure or class.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Stanford | California | United States | 94305 |
| 2 | Research Site | Aurora | Colorado | United States | 80045 |
| 3 | Research Site | New Haven | Connecticut | United States | 06520 |
| 4 | Research Site | Detroit | Michigan | United States | 48201 |
| 5 | Research Site | New York | New York | United States | 10021 |
| 6 | Research Site | Philadelphia | Pennsylvania | United States | 19111 |
| 7 | Research Site | Nashville | Tennessee | United States | 37232 |
| 8 | Research Site | Houston | Texas | United States | 77030 |
| 9 | Research Site | Pierre Benite | France | 69495 | |
| 10 | Research Site | Villejuif | France | 94805 | |
| 11 | Research Site | Frankfurt | Germany | 60488 | |
| 12 | Research Site | Freiburg | Germany | 79106 | |
| 13 | Research Site | Köln | Germany | 50924 | |
| 14 | Research Site | Napoli | Italy | 80131 | |
| 15 | Research Site | Rozzano | Italy | 20089 | |
| 16 | Research Site | Amsterdam | Netherlands | 1066 CX | |
| 17 | Research Site | Rotterdam | Netherlands | 3015 CE | |
| 18 | Research Site | Badajoz | Spain | 06008 | |
| 19 | Research Site | Majadahonda | Spain | 28222 | |
| 20 | Research Site | Valencia | Spain | 46010 | |
| 21 | Research Site | Valencia | Spain | 46026 | |
| 22 | Research Site | Birmingham | United Kingdom | B9 5SS | |
| 23 | Research Site | Edinburgh | United Kingdom | EH4 2XU | |
| 24 | Research Site | Glasgow | United Kingdom | G12 0YN | |
| 25 | Research Site | London | United Kingdom | W12 0NN | |
| 26 | Research Site | London | United Kingdom | W1G 6AD | |
| 27 | Research Site | Manchester | United Kingdom | M20 4BX | |
| 28 | Research Site | Newcastle upon Tyne | United Kingdom | NE7 7DN | |
| 29 | Research Site | Wolverhampton | United Kingdom | WV10 0QP |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Principal Investigator: Fabrice André, Dr, Institut de cancérologie Gustave Roussy
- Study Director: Donal Landers, Dr, AstraZeneca
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00979134
Other Study ID Numbers:
- D2610C00001
First Posted:
Sep 17, 2009
Last Update Posted:
Mar 15, 2019
Last Verified:
Nov 1, 2018
Keywords provided by AstraZeneca
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | First patient enrolled: 21 October 2009 and last patient enrolled: 13 December 2013. This was a multicentre study conducted at a total of 29 centres in 7 countries. |
|---|---|
| Pre-assignment Detail | In Parts A and B, a single dose was followed by a Washout Period of 5 to 10 days before multiple dosing commenced. |
| Arm/Group Title | Part A | Part B | Part C |
|---|---|---|---|
| Arm/Group Description | Dose escalation | Dose expansion phase (80mg bd tablet) | Dose expansion in patients with FGFR gene-amplified tumours |
| Period Title: Overall Study | |||
| STARTED | 43 | 6 | 45 |
| COMPLETED | 10 | 0 | 5 |
| NOT COMPLETED | 33 | 6 | 40 |
Baseline Characteristics
| Arm/Group Title | Part B | Part C (FISH Ratio >= 2) | Part C (FISH Ratio < 2 ) | Part A | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Dose expansion phase (80mg bd tablet) | Dose expansion in patients with FGFR gene-amplified tumours | Dose expansion in patients with FGFR gene-amplified tumours | Dose escalation | Total of all reporting groups |
| Overall Participants | 6 | 33 | 12 | 43 | 94 |
| Age (Years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Years] |
58.7
(8.1)
|
59.5
(10.82)
|
58.2
(11.77)
|
55.8
(10.1)
|
57.59
(10.57)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
3
50%
|
16
48.5%
|
3
25%
|
18
41.9%
|
40
42.6%
|
| Male |
3
50%
|
17
51.5%
|
9
75%
|
25
58.1%
|
54
57.4%
|
Outcome Measures
| Title | AUC(0-infinity) |
|---|---|
| Description | To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. |
| Time Frame | PK samples out to 96 hours "0 to 96 hours post-dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK |
| Arm/Group Title | Part B | Part C (FISH Ratio >= 2) | Part C (FISH Ratio < 2) | Part A |
|---|---|---|---|---|
| Arm/Group Description | Dose expansion phase (80mg bd tablet) | Dose expansion in patients with FGFR gene-amplified tumours | Dose expansion in patients with FGFR gene-amplified tumours | Dose escalation |
| Measure Participants | 6 | 0 | 0 | 42 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
1818
(59.43)
|
2697
(110.8)
|
| Title | Tumour Response (Best Objective Response) - Number of Patients With a Confirmed Response of Partial Response (PR) or Confirmed Response (CR) |
|---|---|
| Description | To obtain a preliminary assessment of the anti tumour activity of AZD4547 by evaluation of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1. Objective response = CR + PR; CR=disappearance of all target lesions and PR is >=30% reduction in sum of longest diameter of target lesions |
| Time Frame | Baseline assessment, then assessment every 6 weeks after start of treatment until objective disease progression. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy/Tumour response: All dosed patients meeting the final FISH 6 score criteria with a baseline tumour assessment and had a FGFR1 FISH ratio ≥2 if the patient was from Part C |
| Arm/Group Title | Part B | Part C (FISH Ratio >= 2) | Part A | Part C (FISH Ratio < 2) |
|---|---|---|---|---|
| Arm/Group Description | Dose expansion phase (80mg bd tablet) | Dose expansion in patients with FGFR gene-amplified tumours | Dose escalation | Dose expansion in patients with FGFR gene-amplified tumours |
| Measure Participants | 6 | 33 | 43 | 12 |
| Number [Patients] |
0
|
1
|
0
|
0
|
| Title | Cmax (ng/mL) |
|---|---|
| Description | To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. |
| Time Frame | PK samples out to 96 hours "0-96 hours post dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK |
| Arm/Group Title | Part B | Part C (FISH Ratio >= 2) | Part A | Part C (FISH Ratio < 2) |
|---|---|---|---|---|
| Arm/Group Description | Dose expansion phase (80mg bd tablet) | Dose expansion in patients with FGFR gene-amplified tumours | Dose escalation | Dose expansion in patients with FGFR gene-amplified tumours |
| Measure Participants | 6 | 0 | 43 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
112.0
(81.47)
|
167.4
(112.1)
|
| Title | Css,Max (ng/mL) |
|---|---|
| Description | To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. |
| Time Frame | PK samples out to 96 hours "0-96 hours post-dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK |
| Arm/Group Title | Part B | Part C (FISH Ratio >= 2) | Part A | Part C (FISH Ratio < 2) |
|---|---|---|---|---|
| Arm/Group Description | Dose expansion phase (80mg bd tablet) | Dose expansion in patients with FGFR gene-amplified tumours | Dose escalation | Dose expansion in patients with FGFR gene-amplified tumours |
| Measure Participants | 6 | 0 | 32 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
289.3
(45.98)
|
297.1
(123.5)
|
| Title | AUC,ss(0-infinity) |
|---|---|
| Description | To characterise the pharmacokinetics (PK) of AZD4547 following a single administration and at steady state after dosing when given orally. |
| Time Frame | PK samples out to 96 hours "0-96 hours post dose" after single dose (in parts A & B only). Steady state PK profile 3 weeks after the start of BD dosing. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK |
| Arm/Group Title | Part B | Part C (FISH Ratio >= 2) | Part C (FISH Ratio < 2) | Part A |
|---|---|---|---|---|
| Arm/Group Description | Dose expansion phase (80mg bd tablet) | Dose expansion in patients with FGFR gene-amplified tumours | Dose expansion in patients with FGFR gene-amplified tumours | Dose escalation |
| Measure Participants | 4 | 0 | 0 | 31 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
2606
(41.32)
|
2337
(125.2)
|
| Title | Number of Patients Who Experienced at Least 1 AE |
|---|---|
| Description | To investigate the safety and tolerability of AZD4547. System organ class (SOC), preferred term (PT), duration and severity all recorded. |
| Time Frame | AEs are monitored from screenng through to 30 day follow up period |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part B | Part C (FISH Ratio >= 2) | Part C (FISH Ratio <2) | Part A |
|---|---|---|---|---|
| Arm/Group Description | Dose expansion phase (80mg bd tablet) | Dose expansion in patients with FGFR gene-amplified tumours | Dose expansion in patients with FGFR gene-amplified tumours | Dose escalation |
| Measure Participants | 6 | 33 | 12 | 43 |
| Number [Participants] |
6
100%
|
33
100%
|
12
100%
|
43
100%
|
| Title | Number of Participants Who Experienced at Least 1 Causally Related AE. |
|---|---|
| Description | To investigate the safety and tolerability of AZD4547. A causally related AE is an AE deemed to be causally related to AZD4547. |
| Time Frame | AEs are continually assessed from screening up to 30 day FU period |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part B | Part C (FISH Ratio >= 2) | Part C (FISH Ratio <2) | Part A |
|---|---|---|---|---|
| Arm/Group Description | Dose expansion phase (80mg bd tablet) | Dose expansion in patients with FGFR gene-amplified tumours | Dose expansion in patients with FGFR gene-amplified tumours | Dose escalation |
| Measure Participants | 6 | 33 | 12 | 43 |
| Number [Participants] |
6
100%
|
31
93.9%
|
10
83.3%
|
42
97.7%
|
| Title | Number of Participants With at Least 1 AE of CTCAE >=G3 |
|---|---|
| Description | To investigate the safety and tolerability of AZD4547 |
| Time Frame | Ongoing up to discontinuation up to 30 day FU. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part B | Part C (FISH Ratio >= 2) | Part C (FISH Ratio <2) | Part A |
|---|---|---|---|---|
| Arm/Group Description | Dose expansion phase (80mg bd tablet) | Dose expansion in patients with FGFR gene-amplified tumours | Dose expansion in patients with FGFR gene-amplified tumours | Dose escalation |
| Measure Participants | 6 | 33 | 12 | 43 |
| Number [Participants] |
1
16.7%
|
16
48.5%
|
5
41.7%
|
17
39.5%
|
| Title | Number of Participants With at Least 1 Causally Related AE of CTCAE >=G3 |
|---|---|
| Description | To investigate the safety and tolerability of AZD4547 |
| Time Frame | Ongoing up to discontinuation up to 30 day FU. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part B | Part C (FISH Ratio >= 2) | Part C (FISH Ratio <2) | Part A |
|---|---|---|---|---|
| Arm/Group Description | Dose expansion phase (80mg bd tablet) | Dose expansion in patients with FGFR gene-amplified tumours | Dose expansion in patients with FGFR gene-amplified tumours | Dose escalation |
| Measure Participants | 6 | 33 | 12 | 43 |
| Number [Participants] |
0
0%
|
8
24.2%
|
3
25%
|
12
27.9%
|
| Title | Number of Participants Who Experienced at Least One SAE |
|---|---|
| Description | To investigate the safety and tolerability of AZD4547. A SAE (Serious Adverse Event) is and AE (adverse Event) which fulfills one of the following criteria that the PI assesses closely such as results in death, immediately life-threatening, requires hospitalisation or prolongation of, results in significant disability, results in birth defect, may jepardise the patient or require intervention to prevent any of the previous outcomes. |
| Time Frame | Serious Adverse Events (SAEs) are continually assessed from Screening up to the end of the 30 day FU period. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part B | Part C (FISH Ratio >= 2) | Part C (FISH Ratio <2) | Part A |
|---|---|---|---|---|
| Arm/Group Description | Dose expansion phase (80mg bd tablet) | Dose expansion in patients with FGFR gene-amplified tumours | Dose expansion in patients with FGFR gene-amplified tumours | Dose escalation |
| Measure Participants | 6 | 33 | 12 | 43 |
| Number [Number of participants] |
1
16.7%
|
10
30.3%
|
3
25%
|
11
25.6%
|
| Title | Number of Participants With at Least 1 Causally Related SAE |
|---|---|
| Description | To investigate the safety and tolerability of AZD4547: SAEs are assessed and deemed as causally related or not to AZD4547 |
| Time Frame | SAEs are continually monitored from screening to end of 30 FU period |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part B | Part C (FISH Ratio >= 2) | Part C (FISH Ratio <2) | Part A |
|---|---|---|---|---|
| Arm/Group Description | Dose expansion phase (80mg bd tablet) | Dose expansion in patients with FGFR gene-amplified tumours | Dose expansion in patients with FGFR gene-amplified tumours | Dose escalation |
| Measure Participants | 6 | 33 | 12 | 43 |
| Number [Number of participants] |
1
16.7%
|
5
15.2%
|
0
0%
|
5
11.6%
|
Adverse Events
| Time Frame | AEs were collected on a continual basis from Screening up until the end of the 28 day follow up period. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Part B | Part C (FISH Ratio >= 2) | Part C (FISH Ratio < 2) | Part A | ||||
| Arm/Group Description | Dose expansion phase (80mg bd tablet) | Dose expansion in patients with FGFR gene-amplified tumours | Dose expansionj in patients with FGFR gene-amplified tumours | Dose escalation | ||||
All Cause Mortality |
||||||||
| Part B | Part C (FISH Ratio >= 2) | Part C (FISH Ratio < 2) | Part A | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Part B | Part C (FISH Ratio >= 2) | Part C (FISH Ratio < 2) | Part A | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/6 (16.7%) | 10/33 (30.3%) | 3/12 (25%) | 11/43 (25.6%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/6 (0%) | 0/33 (0%) | 0/12 (0%) | 1/43 (2.3%) | 1 | |||
| Pericardial effusion | 0/6 (0%) | 1/33 (3%) | 1 | 0/12 (0%) | 1 | 0/43 (0%) | 1 | |
| Eye disorders | ||||||||
| Retinal detachment | 0/6 (0%) | 0/33 (0%) | 0/12 (0%) | 1/43 (2.3%) | 1 | |||
| Chorioretinopathy | 0/6 (0%) | 2/33 (6.1%) | 2 | 0/12 (0%) | 2 | 0/43 (0%) | 2 | |
| Gastrointestinal disorders | ||||||||
| Decreased appetite | 0/6 (0%) | 1/33 (3%) | 1 | 0/12 (0%) | 1 | 0/43 (0%) | 1 | |
| Vomiting | 0/6 (0%) | 1/33 (3%) | 1 | 0/12 (0%) | 1 | 1/43 (2.3%) | 1 | |
| General disorders | ||||||||
| Pyrexia | 0/6 (0%) | 0/33 (0%) | 0/12 (0%) | 1/43 (2.3%) | 1 | |||
| Tumour associated fever | 0/6 (0%) | 0/33 (0%) | 0/12 (0%) | 1/43 (2.3%) | 1 | |||
| General physical health deterioration | 0/6 (0%) | 2/33 (6.1%) | 2 | 1/12 (8.3%) | 1 | 0/43 (0%) | 1 | |
| Asthenia | 0/6 (0%) | 1/33 (3%) | 1 | 1/12 (8.3%) | 1 | 0/43 (0%) | 1 | |
| Hepatobiliary disorders | ||||||||
| Bile duct obstruction | 0/6 (0%) | 1/33 (3%) | 1 | 0/12 (0%) | 1 | 0/43 (0%) | 1 | |
| Infections and infestations | ||||||||
| Pneumonia | 0/6 (0%) | 0/33 (0%) | 1/12 (8.3%) | 1 | 0/43 (0%) | 1 | ||
| Sepsis | 0/6 (0%) | 1/33 (3%) | 1 | 0/12 (0%) | 1 | 1/43 (2.3%) | 1 | |
| Investigations | ||||||||
| ALT increased | 0/6 (0%) | 0/33 (0%) | 0/12 (0%) | 1/43 (2.3%) | 1 | |||
| GGT increased | 0/6 (0%) | 0/33 (0%) | 0/12 (0%) | 1/43 (2.3%) | 1 | |||
| Blood creatinine increased | 1/6 (16.7%) | 1 | 0/33 (0%) | 1 | 0/12 (0%) | 1 | 0/43 (0%) | 1 |
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 0/6 (0%) | 2/33 (6.1%) | 2 | 0/12 (0%) | 2 | 0/43 (0%) | 2 | |
| Hyponatraemia | 0/6 (0%) | 1/33 (3%) | 1 | 0/12 (0%) | 1 | 0/43 (0%) | 1 | |
| Nervous system disorders | ||||||||
| Epilepsy | 0/6 (0%) | 1/33 (3%) | 1 | 0/12 (0%) | 1 | 0/43 (0%) | 1 | |
| Hypotension | 0/6 (0%) | 0/33 (0%) | 1/12 (8.3%) | 1 | 0/43 (0%) | 1 | ||
| Psychiatric disorders | ||||||||
| Delirium | 0/6 (0%) | 0/33 (0%) | 1/12 (8.3%) | 1 | 0/43 (0%) | 1 | ||
| Renal and urinary disorders | ||||||||
| Renal failure | 0/6 (0%) | 0/33 (0%) | 0/12 (0%) | 4/43 (9.3%) | 4 | |||
| Hydronephrosis | 0/6 (0%) | 0/33 (0%) | 0/12 (0%) | 1/43 (2.3%) | 1 | |||
| Nephrolithiasis | 0/6 (0%) | 0/33 (0%) | 0/12 (0%) | 1/43 (2.3%) | 1 | |||
| Pelvi-ureteric obstruction | 0/6 (0%) | 0/33 (0%) | 0/12 (0%) | 1/43 (2.3%) | 1 | |||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnoea | 0/6 (0%) | 2/33 (6.1%) | 2 | 0/12 (0%) | 2 | 1/43 (2.3%) | 1 | |
| Lung disorder | 0/6 (0%) | 0/33 (0%) | 0/12 (0%) | 1/43 (2.3%) | 1 | |||
| Hypoxia | 0/6 (0%) | 1/33 (3%) | 1 | 0/12 (0%) | 1 | 0/43 (0%) | 1 | |
| Pleural effusion | 0/6 (0%) | 1/33 (3%) | 1 | 0/12 (0%) | 1 | 0/43 (0%) | 1 | |
| Respiratory failure | 0/6 (0%) | 1/33 (3%) | 1 | 0/12 (0%) | 1 | 0/43 (0%) | 1 | |
| Social circumstances | ||||||||
| Euthanasia | 0/6 (0%) | 1/33 (3%) | 1 | 0/12 (0%) | 1 | 0/43 (0%) | 1 | |
| Vascular disorders | ||||||||
| Atrial flutter | 0/6 (0%) | 0/33 (0%) | 1/12 (8.3%) | 1 | 0/43 (0%) | 1 | ||
Other (Not Including Serious) Adverse Events |
||||||||
| Part B | Part C (FISH Ratio >= 2) | Part C (FISH Ratio < 2) | Part A | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 33/33 (100%) | 12/12 (100%) | 43/43 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/6 (0%) | 0/33 (0%) | 0/12 (0%) | 4/43 (9.3%) | 4 | |||
| Eye disorders | ||||||||
| Dry eye | 0/6 (0%) | 9/33 (27.3%) | 9 | 0/12 (0%) | 0 | 8/43 (18.6%) | 8 | |
| Oedema peripheral | 0/6 (0%) | 0/33 (0%) | 0/12 (0%) | 7/43 (16.3%) | 7 | |||
| Gastrointestinal disorders | ||||||||
| Constipation | 3/6 (50%) | 3 | 13/33 (39.4%) | 13 | 0/12 (0%) | 0 | 24/43 (55.8%) | 24 |
| Dry mouth | 5/6 (83.3%) | 5 | 15/33 (45.5%) | 15 | 0/12 (0%) | 0 | 18/43 (41.9%) | 18 |
| Stomatis | 5/6 (83.3%) | 5 | 10/33 (30.3%) | 10 | 6/12 (50%) | 6 | 18/43 (41.9%) | 18 |
| Diarrhoea | 3/6 (50%) | 3 | 12/33 (36.4%) | 12 | 4/12 (33.3%) | 4 | 14/43 (32.6%) | 14 |
| Vomiting | 3/6 (50%) | 3 | 10/33 (30.3%) | 10 | 5/12 (41.7%) | 5 | 11/43 (25.6%) | 11 |
| Nausea | 3/6 (50%) | 3 | 9/33 (27.3%) | 9 | 0/12 (0%) | 0 | 11/43 (25.6%) | 11 |
| Abdominal pain | 2/6 (33.3%) | 2 | 0/33 (0%) | 2 | 0/12 (0%) | 2 | 5/43 (11.6%) | 5 |
| Dyspepsia | 1/6 (16.7%) | 1 | 0/33 (0%) | 1 | 0/12 (0%) | 1 | 5/43 (11.6%) | 5 |
| General disorders | ||||||||
| Fatigue | 2/6 (33.3%) | 2 | 13/33 (39.4%) | 13 | 4/12 (33.3%) | 4 | 10/43 (23.3%) | 10 |
| Asthenia | 2/6 (33.3%) | 2 | 4/33 (12.1%) | 4 | 0/12 (0%) | 0 | 9/43 (20.9%) | 9 |
| Pyrexia | 1/6 (16.7%) | 1 | 0/33 (0%) | 1 | 0/12 (0%) | 1 | 5/43 (11.6%) | 5 |
| Investigations | ||||||||
| ALT increased | 0/6 (0%) | 0/33 (0%) | 0/12 (0%) | 4/43 (9.3%) | 4 | |||
| Metabolism and nutrition disorders | ||||||||
| Hyperphosphataemia | 2/6 (33.3%) | 2 | 6/33 (18.2%) | 6 | 0/12 (0%) | 6 | 20/43 (46.5%) | 20 |
| Decreased appetite | 0/6 (0%) | 0 | 11/33 (33.3%) | 11 | 6/12 (50%) | 6 | 12/43 (27.9%) | 12 |
| Ageusia | 4/6 (66.7%) | 4 | 0/33 (0%) | 4 | 0/12 (0%) | 4 | 8/43 (18.6%) | 8 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/12 (0%) | 0 | 13/43 (30.2%) | 13 |
| Nervous system disorders | ||||||||
| Headache | 2/6 (33.3%) | 2 | 0/33 (0%) | 2 | 0/12 (0%) | 2 | 6/43 (14%) | 6 |
| Dysgeusia | 1/6 (16.7%) | 1 | 0/33 (0%) | 1 | 0/12 (0%) | 1 | 5/43 (11.6%) | 5 |
| Dyspepsia | 1/6 (16.7%) | 1 | 0/33 (0%) | 1 | 0/12 (0%) | 1 | 5/43 (11.6%) | 5 |
| Muscle spasms | 1/6 (16.7%) | 1 | 0/33 (0%) | 1 | 0/12 (0%) | 1 | 5/43 (11.6%) | 5 |
| Lethargy | 0/6 (0%) | 0/33 (0%) | 0/12 (0%) | 7/43 (16.3%) | 7 | |||
| Insomnia | 0/6 (0%) | 0/33 (0%) | 0/12 (0%) | 5/43 (11.6%) | 5 | |||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnoea | 0/6 (0%) | 0 | 4/33 (12.1%) | 4 | 0/12 (0%) | 0 | 7/43 (16.3%) | 7 |
| Epistaxis | 0/6 (0%) | 0 | 6/33 (18.2%) | 6 | 0/12 (0%) | 0 | 8/43 (18.6%) | 8 |
| Nasal congestion | 1/6 (16.7%) | 1 | 0/33 (0%) | 1 | 0/12 (0%) | 1 | 5/43 (11.6%) | 5 |
| Dysphonia | 2/6 (33.3%) | 2 | 0/33 (0%) | 2 | 0/12 (0%) | 2 | 4/43 (9.3%) | 4 |
| Breath sounds abnormal | 0/6 (0%) | 5/33 (15.2%) | 5 | 0/12 (0%) | 5 | 0/43 (0%) | 5 | |
| Cough | 0/6 (0%) | 0/33 (0%) | 0/12 (0%) | 10/43 (23.3%) | 10 | |||
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 2/6 (33.3%) | 2 | 8/33 (24.2%) | 8 | 0/12 (0%) | 0 | 21/43 (48.8%) | 21 |
| Dry skin | 1/6 (16.7%) | 1 | 8/33 (24.2%) | 8 | 0/12 (0%) | 0 | 18/43 (41.9%) | 18 |
| Nail disorder | 0/6 (0%) | 0 | 7/33 (21.2%) | 7 | 0/12 (0%) | 0 | 15/43 (34.9%) | 15 |
Limitations/Caveats
Due to early termination no AUC(inf), Cmax, Css,max and AUC,ss for Part C (PK). Data from 33 patients after 22 days of multiple dosing in Part A & limited data for part B only.
1 subject not dosed, so pre-stated subject number 95, total with data 94.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Donal Landers |
|---|---|
| Organization | AstraZeneca |
| Phone | +44 1625 231890 |
| Donal.Landers@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00979134
Other Study ID Numbers:
- D2610C00001
First Posted:
Sep 17, 2009
Last Update Posted:
Mar 15, 2019
Last Verified:
Nov 1, 2018