Acalabrutinib Study With Best Supportive Care in Participants Hospitalized With COVID-19
Study Details
Study Description
Brief Summary
Study D822FC00005 will investigate the Phamacokinetics, Safety and tolerability of Acalabrutinib suspension when delivered via a nasogastric tube and co-administered with a Proton Pump Inhibitor, in the treatment of COVID-19.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
Detailed Description
This study is to support the ongoing clinical development of acalabrutinib (CALQUENCE®) in hospitalized COVID-19 patients. Because many COVID-19 patients may be unable to swallow capsules due to respiratory failure (eg, they may require endotracheal intubation for ventilator support and Naso Gastric tube placement), it is important to have a clinically acceptable method to administer acalabrutinib (capsules) via NG tube. Furthermore, many hospitalized patients are placed on high doses of proton pump inhibitors (PPIs) (also commonly known as antacid medication). This study is designed to determine the Pharmaco Kinetics (effect of body/ bodily systems on the drug), safety and tolerability of acalabrutinib suspension, when coadministered with a PPI, in participants with confirmed SARS-CoV-2 infection requiring hospitalization due to respiratory failure, attributable to COVID-19 pneumonia and who have an Nasogastric (NG) tube in place.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Other: Single Arm Single Arm |
Drug: Acalabrutinib
Acalabrutinib (CALQUENCE®) is a covalent BTK inhibitor
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Area Under the Concentration-time Curve From 0 to 12 Hours (AUC12h) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2 (Day 2), and Visit 3 (Day 5) [pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1 on Day 1, visit 2 on Day 2 and visit 3 on Day 5]
To summarize the PK parameter AUC12h of Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC + PPI
- Area Under the Concentration-time Curve From 0 to Time to Last Quantifiable Concentration (AUClast) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2 (Day 2), and Visit 3 (Day 5) [pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1 on Day 1, visit 2 on Day 2 and visit 3 on Day5]
To summarize the PK parameter AUClast for Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC +PPI
- Maximum Observed Plasma Concentration (Cmax) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2(Day2) and Visit 3 (Day 5) [pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1(Day 1), visit 2(Day 2) and visit 3(Day 5)]
To summarize the PK parameter Cmax of Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC +PPI
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participant or legally authorized representative must be able to understand the purpose and risks of the study and provide written informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).
-
Participants who are hospitalized with coronavirus (SARS-CoV-2) infection, confirmed by PCR test or other commercial or public health assay in any specimen, as documented by either of the following:
-
PCR positive in sample collected < 72 hours prior to first dose, OR
-
PCR positive in sample collected ≥ 72 hours prior to first dose (but no more than 14 days prior to first dose), documented inability to obtain a repeat sample (eg, due to lack of testing supplies, limited testing capacity, results taking > 24 hours, etc), AND progressive disease suggestive of ongoing SARS-CoV-2 infection 3 Evidence of respiratory failure attributable to COVID-19 pneumonia (documented radiographically) before enrollment 4 Nasogastric tube or other types of oral or percutaneous gastric feeding tube; placement must be radiographically confirmed and expected to remain in place, as judged by the investigator, for a minimum of 3 days after study enrolment.
5 Has received treatment with PPIs (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole) for a minimum of 24 hours immediately prior to enrollment; any PPI will be permitted, provided it meets the minimum equivalent daily dose of 20 mg rabeprazole.
Exclusion Criteria:
-
Any serious and uncorrectable medical condition or abnormality of clinical laboratory tests that, in the Investigator's judgment, precludes the participant's safe participation in and completion of the study.
-
In the opinion of the Investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments.
-
Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
-
Received BTK inhibitor within 7 days before enrollment.
-
Requires or is receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days prior to enrollment. Other anticoagulants are permitted.
-
Participants on dual antiplatelet and therapeutic anticoagulant therapy (eg, aspirin and therapeutic doses of low molecular weight heparin are not allowed; however, aspirin and prophylactic/ low doses of low-molecular-weight heprin are allowed).
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Research Site | Porto Alegre | Brazil | 90035-003 | |
2 | Research Site | Ribeirão Preto | Brazil | 14051-140 | |
3 | Research Site | Sao Paulo | Brazil | 01321-001 | |
4 | Research Site | Sao Paulo | Brazil | 01323-903 |
Sponsors and Collaborators
- Acerta Pharma BV
- AstraZeneca
Investigators
None specified.Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- D822FC00005
Study Results
Participant Flow
Recruitment Details | Approximately 20 participants were planned to be enrolled to have at least 16 evaluable participants. |
---|---|
Pre-assignment Detail | The study enrollment was terminated early due to the termination of the Calquence COVID-19 Clinical development program (LSPC Nov 2020) |
Arm/Group Title | Acalabrutinib + BSC + PPI |
---|---|
Arm/Group Description | Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment. |
Period Title: Overall Study | |
STARTED | 9 |
COMPLETED | 7 |
NOT COMPLETED | 2 |
Baseline Characteristics
Arm/Group Title | Acalabrutinib + BSC + PPI |
---|---|
Arm/Group Description | Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment. |
Overall Participants | 9 |
Age (Years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [Years] |
61.3
(10.7)
|
Age, Customized (Number) [Number] | |
< 65 years |
4
44.4%
|
>= 65 years |
5
55.6%
|
Sex: Female, Male (Count of Participants) | |
Female |
4
44.4%
|
Male |
5
55.6%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
7
77.8%
|
Not Hispanic or Latino |
2
22.2%
|
Unknown or Not Reported |
0
0%
|
Race/Ethnicity, Customized (Number) [Number] | |
WHITE |
7
77.8%
|
BLACK OR AFRICAN AMERICAN |
2
22.2%
|
AMERICAN INDIAN OR ALASKA NATIVE |
0
0%
|
ASIAN |
0
0%
|
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER |
0
0%
|
OTHER |
0
0%
|
NOT REPORTED |
0
0%
|
Outcome Measures
Title | Area Under the Concentration-time Curve From 0 to 12 Hours (AUC12h) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2 (Day 2), and Visit 3 (Day 5) |
---|---|
Description | To summarize the PK parameter AUC12h of Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC + PPI |
Time Frame | pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1 on Day 1, visit 2 on Day 2 and visit 3 on Day 5 |
Outcome Measure Data
Analysis Population Description |
---|
Here, number analyzed in each row signifies only the participants with available data that were analyzed for each Acalabrutinib and ACP-5862 analytes. |
Arm/Group Title | Acalabrutinib + BSC + PPI, Visit 1 on Day 1 | Acalabrutinib + BSC + PPI, Visit 2 on Day 2 | Acalabrutinib + BSC + PPI, Visit 3 on Day 5 |
---|---|---|---|
Arm/Group Description | Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 1 on Day 1. | Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 2 on Day 2. | Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 3 on Day 5. |
Measure Participants | 9 | 9 | 7 |
Acalabrutinib |
524.7
(86.5)
|
496.5
(58.0)
|
201.1
(95.3)
|
ACP-5862 |
832.8
(29.3)
|
1228.0
(35.1)
|
867.1
(43.1)
|
Title | Area Under the Concentration-time Curve From 0 to Time to Last Quantifiable Concentration (AUClast) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2 (Day 2), and Visit 3 (Day 5) |
---|---|
Description | To summarize the PK parameter AUClast for Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC +PPI |
Time Frame | pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1 on Day 1, visit 2 on Day 2 and visit 3 on Day5 |
Outcome Measure Data
Analysis Population Description |
---|
Here, number analyzed in each row signifies only the participants with available data that were analyzed for each Acalabrutinib and ACP-5862 analytes. |
Arm/Group Title | Acalabrutinib + BSC + PPI, Visit 1 on Day 1 | Acalabrutinib + BSC + PPI, Visit 2 on Day 2 | Acalabrutinib + BSC + PPI, Visit 3 on Day 5 |
---|---|---|---|
Arm/Group Description | Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment. | Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 2 on Day 2. | Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment on visit 3 on Day 5. |
Measure Participants | 9 | 9 | 7 |
Acalabrutinib |
490.1
(64.8)
|
493.7
(58.4)
|
193.7
(96.6)
|
ACP-5862 |
731.0
(38.4)
|
1228.0
(35.1)
|
827.9
(46.2)
|
Title | Maximum Observed Plasma Concentration (Cmax) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2(Day2) and Visit 3 (Day 5) |
---|---|
Description | To summarize the PK parameter Cmax of Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC +PPI |
Time Frame | pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1(Day 1), visit 2(Day 2) and visit 3(Day 5) |
Outcome Measure Data
Analysis Population Description |
---|
Here, number analyzed in each row signifies only the participants with available data that were analyzed for each Acalabrutinib and ACP-5862 analytes. |
Arm/Group Title | Acalabrutinib + BSC + PPI, Visit 1 on Day 1 | Acalabrutinib + BSC + PPI, Visit 2 on Day 2 | Acalabrutinib + BSC + PPI, Visit 3 on Day 5 |
---|---|---|---|
Arm/Group Description | Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 1 on Day 1. | Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 2 on Day 2. | Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 3 on Day 5. |
Measure Participants | 9 | 9 | 7 |
Acalabrutinib |
297.0
(56.7)
|
307.9
(51.3)
|
167.1
(88.7)
|
ACP-5862 |
213.1
(62.9)
|
316.9
(38.5)
|
324.2
(47.6)
|
Adverse Events
Time Frame | 2 months | |
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Acalabrutinib + BSC + PPI | |
Arm/Group Description | Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment. | |
All Cause Mortality |
||
Acalabrutinib + BSC + PPI | ||
Affected / at Risk (%) | # Events | |
Total | 2/9 (22.2%) | |
Serious Adverse Events |
||
Acalabrutinib + BSC + PPI | ||
Affected / at Risk (%) | # Events | |
Total | 5/9 (55.6%) | |
Infections and infestations | ||
Device related infection | 1/9 (11.1%) | 1 |
Pneumonia | 1/9 (11.1%) | 1 |
Pneumonia bacterial | 2/9 (22.2%) | 2 |
Investigations | ||
Transaminases increased | 1/9 (11.1%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||
Pulmonary embolism | 1/9 (11.1%) | 1 |
Vascular disorders | ||
Hypotension | 1/9 (11.1%) | 1 |
Other (Not Including Serious) Adverse Events |
||
Acalabrutinib + BSC + PPI | ||
Affected / at Risk (%) | # Events | |
Total | 9/9 (100%) | |
Blood and lymphatic system disorders | ||
Anaemia | 5/9 (55.6%) | 6 |
Lymphopenia | 2/9 (22.2%) | 2 |
Thrombocytopenia | 1/9 (11.1%) | 3 |
Gastrointestinal disorders | ||
Abdominal distension | 2/9 (22.2%) | 2 |
Constipation | 1/9 (11.1%) | 1 |
Diarrhoea | 1/9 (11.1%) | 1 |
Vomiting | 1/9 (11.1%) | 1 |
Infections and infestations | ||
Fungal infection | 1/9 (11.1%) | 1 |
Infection | 1/9 (11.1%) | 1 |
Klebsiella infection | 1/9 (11.1%) | 1 |
Lower respiratory tract infection bacterial | 1/9 (11.1%) | 1 |
Pneumonia | 2/9 (22.2%) | 2 |
Pneumonia bacterial | 2/9 (22.2%) | 2 |
Urinary tract infection | 1/9 (11.1%) | 1 |
Investigations | ||
Alanine aminotransferase increased | 2/9 (22.2%) | 2 |
Aspartate aminotransferase increased | 2/9 (22.2%) | 3 |
Hepatic enzyme increased | 1/9 (11.1%) | 1 |
Metabolism and nutrition disorders | ||
Hyperglycaemia | 1/9 (11.1%) | 1 |
Hypernatraemia | 2/9 (22.2%) | 3 |
Hypophosphataemia | 2/9 (22.2%) | 2 |
Type 2 diabetes mellitus | 1/9 (11.1%) | 1 |
Nervous system disorders | ||
Peripheral motor neuropathy | 2/9 (22.2%) | 3 |
Polyneuropathy | 1/9 (11.1%) | 1 |
Psychiatric disorders | ||
Anxiety | 1/9 (11.1%) | 1 |
Renal and urinary disorders | ||
Acute kidney injury | 1/9 (11.1%) | 1 |
Renal impairment | 1/9 (11.1%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||
Haemoptysis | 1/9 (11.1%) | 1 |
Laryngospasm | 1/9 (11.1%) | 1 |
Organising pneumonia | 1/9 (11.1%) | 1 |
Pulmonary embolism | 1/9 (11.1%) | 1 |
Skin and subcutaneous tissue disorders | ||
Dermatitis | 1/9 (11.1%) | 1 |
Vascular disorders | ||
Haematoma | 1/9 (11.1%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
PI shall provide copies of any materials relating to the Study, or the Developed Technologies that either intends to publish or make any presentations relating to, at least 30 days in advance of publication, submission or presentation. PI shall not include in or shall remove from any proposed publication of any Confidential Information, errors or inaccuracies; and shall withhold publication, submission for publication or presentation for 90 days from the date the Company receives the material.
Results Point of Contact
Name/Title | Study Information Center |
---|---|
Organization | AstraZeneca |
Phone | 1-877-240-9479 |
information.center@astrazeneca.com |
- D822FC00005