COVID-19
Conditions
Keywords
2019 novel coronavirus disease, Acalabrutinib, Btk inhibitor
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.
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.
Interventions
DRUGAcalabrutinib
Acalabrutinib (CALQUENCE®) is a covalent BTK inhibitor
Sponsors
AstraZeneca
Acerta Pharma BV
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single group multi dose study. Participants to receive Acalabrutinib + PPI and Best Supportive Care.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. 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). 2. 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: 1. PCR positive in sample collected \< 72 hours prior to first dose, OR 2. 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
1. 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. 2. In the opinion of the Investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments. 3. 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. 4. Received BTK inhibitor within 7 days before enrollment. 5. Requires or is receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days prior to enrollment. Other anticoagulants are permitted. 6. 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Brazil
Participant flow
Recruitment details
Approximately 20 participants were planned to be enrolled to have at least 16 evaluable participants.
Pre-assignment details
The study enrollment was terminated early due to the termination of the Calquence COVID-19 Clinical development program (LSPC Nov 2020)
Participants by arm
| Arm | Count |
|---|---|
| Acalabrutinib + BSC + PPI Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment. | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
Baseline characteristics
| Characteristic | Acalabrutinib + BSC + PPI |
|---|---|
| Age, Continuous | 61.3 Years STANDARD_DEVIATION 10.7 |
| Age, Customized < 65 years | 4 Participants |
| Age, Customized >= 65 years | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized AMERICAN INDIAN OR ALASKA NATIVE | 0 Participants |
| Race/Ethnicity, Customized ASIAN | 0 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 2 Participants |
| Race/Ethnicity, Customized NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER | 0 Participants |
| Race/Ethnicity, Customized NOT REPORTED | 0 Participants |
| Race/Ethnicity, Customized OTHER | 0 Participants |
| Race/Ethnicity, Customized WHITE | 7 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 9 |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 5 / 9 |
Outcome results
Primary
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)
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
Population: Here, number analyzed in each row signifies only the participants with available data that were analyzed for each Acalabrutinib and ACP-5862 analytes.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Acalabrutinib + BSC + PPI, Visit 1 on Day 1 | 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) | Acalabrutinib | 524.7 h·ng/mL | Geometric Coefficient of Variation 86.5 |
| Acalabrutinib + BSC + PPI, Visit 1 on Day 1 | 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) | ACP-5862 | 832.8 h·ng/mL | Geometric Coefficient of Variation 29.3 |
| Acalabrutinib + BSC + PPI, Visit 2 on Day 2 | 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) | Acalabrutinib | 496.5 h·ng/mL | Geometric Coefficient of Variation 58 |
| Acalabrutinib + BSC + PPI, Visit 2 on Day 2 | 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) | ACP-5862 | 1228.0 h·ng/mL | Geometric Coefficient of Variation 35.1 |
| Acalabrutinib + BSC + PPI, Visit 3 on Day 5 | 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) | ACP-5862 | 867.1 h·ng/mL | Geometric Coefficient of Variation 43.1 |
| Acalabrutinib + BSC + PPI, Visit 3 on Day 5 | 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) | Acalabrutinib | 201.1 h·ng/mL | Geometric Coefficient of Variation 95.3 |
Primary
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)
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
Population: Here, number analyzed in each row signifies only the participants with available data that were analyzed for each Acalabrutinib and ACP-5862 analytes.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Acalabrutinib + BSC + PPI, Visit 1 on Day 1 | 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) | Acalabrutinib | 490.1 h·ng/mL | Geometric Coefficient of Variation 64.8 |
| Acalabrutinib + BSC + PPI, Visit 1 on Day 1 | 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) | ACP-5862 | 731.0 h·ng/mL | Geometric Coefficient of Variation 38.4 |
| Acalabrutinib + BSC + PPI, Visit 2 on Day 2 | 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) | Acalabrutinib | 493.7 h·ng/mL | Geometric Coefficient of Variation 58.4 |
| Acalabrutinib + BSC + PPI, Visit 2 on Day 2 | 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) | ACP-5862 | 1228.0 h·ng/mL | Geometric Coefficient of Variation 35.1 |
| Acalabrutinib + BSC + PPI, Visit 3 on Day 5 | 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) | Acalabrutinib | 193.7 h·ng/mL | Geometric Coefficient of Variation 96.6 |
| Acalabrutinib + BSC + PPI, Visit 3 on Day 5 | 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) | ACP-5862 | 827.9 h·ng/mL | Geometric Coefficient of Variation 46.2 |
Primary
Maximum Observed Plasma Concentration (Cmax) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2(Day2) and Visit 3 (Day 5)
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)
Population: Here, number analyzed in each row signifies only the participants with available data that were analyzed for each Acalabrutinib and ACP-5862 analytes.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Acalabrutinib + BSC + PPI, Visit 1 on Day 1 | Maximum Observed Plasma Concentration (Cmax) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2(Day2) and Visit 3 (Day 5) | Acalabrutinib | 297.0 ng/mL | Geometric Coefficient of Variation 56.7 |
| Acalabrutinib + BSC + PPI, Visit 1 on Day 1 | Maximum Observed Plasma Concentration (Cmax) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2(Day2) and Visit 3 (Day 5) | ACP-5862 | 213.1 ng/mL | Geometric Coefficient of Variation 62.9 |
| Acalabrutinib + BSC + PPI, Visit 2 on Day 2 | Maximum Observed Plasma Concentration (Cmax) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2(Day2) and Visit 3 (Day 5) | Acalabrutinib | 307.9 ng/mL | Geometric Coefficient of Variation 51.3 |
| Acalabrutinib + BSC + PPI, Visit 2 on Day 2 | Maximum Observed Plasma Concentration (Cmax) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2(Day2) and Visit 3 (Day 5) | ACP-5862 | 316.9 ng/mL | Geometric Coefficient of Variation 38.5 |
| Acalabrutinib + BSC + PPI, Visit 3 on Day 5 | Maximum Observed Plasma Concentration (Cmax) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2(Day2) and Visit 3 (Day 5) | Acalabrutinib | 167.1 ng/mL | Geometric Coefficient of Variation 88.7 |
| Acalabrutinib + BSC + PPI, Visit 3 on Day 5 | Maximum Observed Plasma Concentration (Cmax) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2(Day2) and Visit 3 (Day 5) | ACP-5862 | 324.2 ng/mL | Geometric Coefficient of Variation 47.6 |