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| Name | Class |
|---|---|
| Rockefeller University | OTHER |
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This study is 'A Randomized Phase 1 Double Blind Placebo Controlled, Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Inhaled Aerosolized Hydroxychloroquine Sulfate in Healthy Adult Volunteers.' The primary objectives are as follows:
Secondary objectives:
• To characterize pharmacokinetics (PK) of single dose AHCQ in healthy individuals.
Study Design:
This is a randomized, double-blind placebo-controlled Phase 1 single-dose dose-escalation study to assess the safety, tolerability and PK of oral inhalation of AHCQ in healthy participants.
Escalating single doses of AHCQ will be studied in healthy participants. The study drug will be administered by inhalation through the mouth, and participants will be encouraged to exhale through the nose. The study drug, AHCQ, will be administered starting at an initial dose of 20 mg (Cohort A1, 1 mL of 20 mg/mL AHCQ solution) with a proposed subsequent doses of 50 mg (Cohort A2, 1 mL of 50 mg/mL AHCQ).
Number of Participants (Planned):
Two dose levels are planned to be evaluated. Each cohort will comprise 8 participants (6 active, 2 placebo). Therefore, 16 participants will initially be planned to be enrolled in the study. Additional participants may be enrolled if one or more enrolled participants do not complete the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hydroxychloroquine Sulfate | Active Comparator | The study drug AHCQ will be administered by inhalation through the mouth. The starting dose will be 20 mg (Cohort A1) with a proposed subsequent dose of 50 mg (Cohort A2). At each dose level 8 participants (including at least 3 female participants and 3 participants older than 50 years old) will be enrolled. Six participants will receive the active study drug and 2 participants will receive placebo. |
|
| Placebo | Placebo Comparator | Placebo will be administered by inhalation through the mouth. It will be administered in both Cohort A1 and Cohort A2. Six participants will receive the active study drug and 2 participants will receive placebo. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aerolized Hydroxychloroquine Sulfate | Drug | sterile AHCQ 100 mg/mL for inhalation, is a clear solution packaged in clear glass vials and stored at room temperature. |
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| Measure | Description | Time Frame |
|---|---|---|
| Incidences of treatment-emergent adverse events (TEAEs) as assessed by TGSHAAV (September 2007) or CTCAE version 5.0 | TEAEs (defined as AEs with onset after study drug administration or existing AEs that worsen in severity after study drug administration) | after treatment (Day 1) through to Day 30 |
| Change from baseline in clinical laboratory test results for CBC with differential | Blood sample collected for CBC with differential will be assessed from baseline (at screening) | Screening and Day 8 |
| Incidence of abnormal laboratory test results for CBC with differential at Screening | Screening blood sample collected for CBC with differential, counting the number of abnormal clinical tests | Screening |
| Incidence of abnormal laboratory test results for CBC with differential - Day 8 | Day 8 blood sample collected for CBC with differential | Day 8 |
| Changes from baseline for blood glucose | Blood sample collected for blood glucose and measured with a glucometer | Screening and Day 1 |
| Incidence of abnormal laboratory test results for chemistry -Screening | Blood sample collected for chemistry panel (albumin, total protein, ALP, ALT, AST, direct and indirect bilirubin, GGT, BUN, creatinine, glucose, bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, and LDH) | Screening |
| Incidence of abnormal laboratory tests results for chemistry - Day 8 |
| Measure | Description | Time Frame |
|---|---|---|
| HCQ concentration in whole blood versus time profiles | Blood samples for PK analysis will be collected via indwelling catheter or via direct venipuncture. | Day 1 pre-dose (time 0) and +2, +3, +5, and +15 minutes after dose, and also +1, +2, +4 and +6 hours post-dose completion. Day 2 (+24±4 hours post dose) and Day 8. |
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Inclusion Criteria:
Willing and able to give written informed consent.
Males or females aged ≥18 years old.
Good general health as determined by no acute illness and no clinically significant abnormal findings on medical history, vital signs, laboratory tests, or physical examination at screening that, in the opinion of the PI, would interfere with study drug administration, jeopardize the safety of the study participant, or impact the validity of the study results; participants with stable chronic illness are allowed at the discretion of the PI.
An interpretable 12-lead ECG with a corrected QT (QTc) interval ≤450 ms, according to Bazett's formula, without evidence of clinically significant abnormal findings.
Normal FEV1/FVC ratio, defined as any value above 0.7 or above the lower 5th percentile of normal AND FEV1 >80% of predicted or above the lower 5th percentile of normal.
Pulse oximetry 02 saturation ≥95% in room air.
Negative test result for COVID-19 within 7 days of Day 1 AND concurrent with local hospital policy:
Females of child-bearing potential must be non-pregnant, non-lactating, have a negative urine pregnancy test at screening, and agree to use an acceptable form of birth control for 200 days after the last administration of the study drug. Females are considered of non-childbearing potential if they are postmenopausal (last menstrual period at least 1 year before screening) or have been surgically sterilized (documented hysterectomy, tubal ligation, or bilateral oophorectomy) for at least 6 months at screening.
Willing to comply with protocol-defined procedures and complete all study visits.
Willing to use the Inhalation System and exhale through the nose.
Adequate venous access in the left or right arm to allow collection of required blood samples.
Participant understands and communicates in English.
Serum Potassium level ≥3.5 mEq/L, Serum Magnesium level ≥1.5 mg/dL, and Serum Calcium ≥8.5 mg/dL.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ohad S Bentur, MD, MHA | Rockefeller University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Rockefeller University | New York | New York | 10065 | United States |
There is no plan to make IPD available to other researchers.
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This is a randomized, double-blind placebo-controlled Phase 1 single-dose dose-escalation study to assess the safety, tolerability and PK of oral inhalation of AHCQ in healthy participants.
A sentinel dose strategy will be employed and the decision to escalate to the next dose level, or deescalate or stop the study, will be based on review and analysis of all available blinded safety and tolerability data by the Safety Review Committee (SRC), which will make a recommendation to the Sponsor and the Sponsor will inform the PI of the recommendation.
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| Placebo | Other | The placebo product and diluent solution is sodium chloride inhalation solution, United States Pharmacopeia (USP) 0.9%. |
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Blood sample collected for chemistry panel (albumin, total protein, ALP, ALT, AST, direct and indirect bilirubin, GGT, BUN, creatinine, glucose, bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, and LDH) |
| Day 8 |
| Incidence of abnormal laboratory tests results for urinalysis - Screening | Collection of urine sample to test pH, specific gravity, protein, glucose, ketones, urobilinogen, bilirubin, leukocyte esterase, squamous cells, epithelial cells, clarity, bacteria, blood | Screening |
| Incidence of abnormal laboratory tests results for urinalysis- Day 8 | Collection of urine sample to test pH, specific gravity, protein, glucose, ketones, urobilinogen, bilirubin, leukocyte esterase, squamous cells, epithelial cells, clarity, bacteria, blood | Day 8 |
| Changes in vital signs from baseline (pre-dose) - respiratory rate | The Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials (September 2007) (TGSHAAV) will be used as the primary criteria for assessment of clinical abnormalities. Mild (17-20 breaths per minute) to Potentially Life Threatening (intubation) | Screening, Day 1, Day 2 and Day 8 |
| Changes in vital signs from baseline (pre-dose)- temperature | Oral temperature | Screening, Day 1, Day 2 and Day 8 |
| Changes in vital signs from baseline (pre-dose) - seated blood pressure | Systolic and diastolic blood pressure | Screening, Day 1, Day 2 and Day 8 |
| Changes in vital signs from baseline (pre-dose) - pulse | Heart rate measure by radial pulse rate (beats/min) | Screening, Day 1, Day 2 and Day 8 |
| Changes in vital signs from baseline (pre-dose) - O2 saturation | O2 saturation (%), measured by pulse oximeter. Graded as per TGSHAAV (September 2007) from Moderate (pulse oximeter <92%) to Potentially Life Threatening (Life-threatening airway compromise; urgent intervention indicated) | Screening, Day 1, Day 2 and Day 8 |
| Incidence of abnormal and physical examinations findings during Screening- general appearance | Physical exam by clinician. A directed physical examination will be conducted | Screening |
| Incidence of abnormal and physical examinations findings on Day 1 - general appearance | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 1 |
| Incidence of abnormal and physical examinations findings on Day 2- general appearance | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 2 |
| Incidence of abnormal and physical examinations findings on Day 8- general appearance | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 8 |
| Incidence of abnormal and physical examinations findings during Screening- neurological | Physical exam by clinician. A directed physical examination will be conducted | Screening |
| Incidence of abnormal and physical examinations findings on Day 1- neurological | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 1 |
| Incidence of abnormal and physical examinations findings on Day 2- neurological | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 2 |
| Incidence of abnormal and physical examinations findings on Day 8- neurological | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 8 |
| Incidence of abnormal and physical examinations findings during Screening - heart/cardiovascular | Physical exam by clinician. A directed physical examination will be conducted | Screening |
| Incidence of abnormal and physical examinations findings on Day 1 - heart/cardiovascular | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 1 (pre-dose, within 3 hours of dose) |
| Incidence of abnormal and physical examinations findings on Day 2 - heart/cardiovascular | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 2 |
| Incidence of abnormal and physical examinations findings on Day 8 - heart/cardiovascular | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 8 |
| Incidence of abnormal and physical examinations findings during Screening - lungs | Physical exam by clinician. A directed physical examination will be conducted | Screening |
| Incidence of abnormal and physical examinations findings on Day 1 - lungs | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 1 |
| Incidence of abnormal and physical examinations findings on Day 2 - lungs | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 2 |
| Incidence of abnormal and physical examinations findings on Day 8 - lungs | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 8 |
| Incidence of abnormal and physical examinations findings during Screening- abdomen | Physical exam by clinician. A directed physical examination will be conducted | Screening |
| Incidence of abnormal and physical examinations findings on Day 1 - abdomen | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 1 |
| Incidence of abnormal and physical examinations findings on Day 2- abdomen | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 2 |
| Incidence of abnormal and physical examinations findings on Day 8- abdomen | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 8 |
| Incidence of abnormal and physical examinations findings during screening- endocrine | Physical exam by clinician. A directed physical examination will be conducted | Screening |
| Incidence of abnormal and physical examinations findings on Day 1 - endocrine | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 1 |
| Incidence of abnormal and physical examinations findings on Day 2- endocrine | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 2 |
| Incidence of abnormal and physical examinations findings on Day 8- endocrine | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 8 |
| Incidence of abnormal and physical examinations findings during Screening- extremities | Physical exam by clinician. A directed physical examination will be conducted | Screening |
| Incidence of abnormal and physical examinations findings on Day 1- extremities | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 1 |
| Incidence of abnormal and physical examinations findings on Day 2- extremities | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 2 |
| Incidence of abnormal and physical examinations findings on Day 8- extremities | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 8 |
| Incidence of abnormal and physical examinations findings during Screening- lymphatic | Physical exam by clinician. A directed physical examination will be conducted | Screening |
| Incidence of abnormal and physical examinations findings on Day 1- lymphatic | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 1 |
| Incidence of abnormal and physical examinations findings on Day 2 - lymphatic | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 2 |
| Incidence of abnormal and physical examinations findings on Day 8- lymphatic | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 8 |
| Incidence of abnormal and physical examinations findings during screening - skin | A directed physical examination will be conducted | Screening |
| Incidence of abnormal and physical examinations findings on Day 1 - skin | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 1 |
| Incidence of abnormal and physical examinations findings on Day 2 - skin | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 2 |
| Incidence of abnormal and physical examinations findings on Day 8 - skin | Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted | Day 8 |
| Changes from baseline for pulmonary function tests (PFTs) - FEV1 | Pulmonary function testing and recording of FEV1, both actual and percent predicted | Screening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8. |
| Changes from baseline for pulmonary function tests (PFTs) - FVC | Pulmonary function testing and recording of FVC, , both actual and percent predicted | Screening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8. |
| Changes from baseline for pulmonary function tests (PFTs) - FEV1/FVC | Pulmonary function testing and recording of FEV1/FVC | creening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8. |
| Changes from baseline for ECG readings - QT interval | The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval (msec) will be the assessment parameter. | Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8. |
| Changes from baseline for ECG readings - QTcB Interval | The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QTcB interval (msec) will be the assessment parameter. | Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8. |
| Changes from baseline for ECG readings - QRS duration | The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QRS duration (msec) will be the assessment parameter. | Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8. |
| Changes from baseline for ECG readings - PR interval | The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG PR interval (msec) will be the assessment parameter. | Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8. |
| Changes from baseline for ECG readings - heart rate | The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG heart rate (beats/min) will be the assessment parameter. | Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8. |
| Incidence of abnormal ECG - Screening | The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval will be the assessment parameter. | Screening |
| Incidence of abnormal ECG- Day 1 | The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval will be the assessment parameter. | Day 1 pre-dose (within 3 hours of dose) and +2 and +6 hours |
| Incidence of abnormal ECG - Day 2 | The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval will be the assessment parameter. | Days 2 |
| Incidence of abnormal ECG - Day 8 | The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval will be the assessment parameter. | Days 8. |
| ID | Term |
|---|---|
| D018352 | Coronavirus Infections |
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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