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| ID | Type | Description | Link |
|---|---|---|---|
| DMID18-0013 | Other Identifier | NIAID | |
| 272201300017C-18-0-1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
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This is a placebo-controlled, randomized, double-blind study to evaluate the pharmacokinetics of galidesivir following administration of single doses by IV infusion
This single ascending dose study will evaluate the safety, tolerability, and PK of single doses of galidesivir vs. placebo administered as IV infusions in healthy subjects enrolled in up to four dose cohorts of 8 subjects each. A single dose of study drug will be administered per cohort: 6 subjects will receive galidesivir IV, and 2 subjects will receive matching placebo.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Galidesivir | Experimental | Galidesivir IV infusion |
|
| placebo | Placebo Comparator | Placebo IV infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| galidesivir | Drug | galidesivir IV infusion |
| |
| placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Galidesivir Safety and Tolerability, as Measured by the Number of Participants Experiencing Adverse Events. | Any event reported on the subject's study record that occurred on or after the initiation of study drug was defined as treatment emergent (TEAE). | AEs were assessed and recorded from the time of signing the ICF through to the appropriate follow-up period, up to 23 days from IMP dosing on Day 1. |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma PK - Galidesivir Cmax (Maximum Observed Concentration of Drug) | Serial blood samples for PK assessment of plasma galidesivir were collected at the following time points:
Cmax for galidesivir was estimated using non compartmental methods with Phoenix® WinNonlin® v8.1 or higher (Certara, Inc.). |
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Key Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Daniel Dickerson, MD, PhD | PRA Health Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PRA Health Sciences | Lenexa | Kansas | 66219 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35182042 | Derived | Mathis A, Collins D, Dobo S, Walling DM, Sheridan WP, Taylor R. Pharmacokinetics and Safety of the Nucleoside Analog Antiviral Drug Galidesivir Administered to Healthy Adult Subjects. Clin Pharmacol Drug Dev. 2022 Apr;11(4):467-474. doi: 10.1002/cpdd.1037. Epub 2022 Feb 19. |
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A single dose of study drug was administered to subjects in each of cohorts 1 to 4. In each cohort, 6 subjects received galidesivir and 2 subjects received matching placebo.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | single placebo IV infusion |
| FG001 | 5 mg/kg Galidesivir | Single IV infusion 5 mg/kg galidesivir |
| FG002 | 10 mg/kg Galidesivir | Single IV infusion 10 mg/kg galidesivir |
| FG003 | 15 mg/kg Galidesivir | Single IV infusion 15 mg/kg galidesivir |
| FG004 | 20 mg/kg Galidesivir | Single IV infusion 20 mg/kg galidesivir |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The safety population included all randomized subjects who received any amount of study drug (i.e. a partial infusion). Subjects were analyzed according to the treatment received. The safety population was used for analyses of demographics.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | single placebo IV infusion |
| BG001 | 5 mg/kg Galidesivir | Single IV infusion 5 mg/kg galidesivir |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Galidesivir Safety and Tolerability, as Measured by the Number of Participants Experiencing Adverse Events. | Any event reported on the subject's study record that occurred on or after the initiation of study drug was defined as treatment emergent (TEAE). | The safety population included all randomized subjects who received any amount of study drug (i.e. a partial infusion). | Posted | Number | participants | AEs were assessed and recorded from the time of signing the ICF through to the appropriate follow-up period, up to 23 days from IMP dosing on Day 1. |
|
AEs were assessed and recorded from the time of signing the ICF through to the appropriate follow-up visit, up to 23 days from IMP dosing on Day 1. All AEs were graded for severity using the modified 2014 DMID Adult Toxicity Grading Scale. Any AEs not covered by the DMID criteria were assessed and classified into 1 of 3 clearly defined categories (mild, moderate, or severe).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | single placebo IV infusion | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| gastrooesophageal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | BioCryst Pharmaceuticals Inc | +1 919-859-1302 | clinicaltrials@biocryst.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 11, 2019 | Jun 14, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 10, 2019 | Jun 14, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D008379 | Marburg Virus Disease |
| ID | Term |
|---|---|
| D006482 | Hemorrhagic Fevers, Viral |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C517546 | galidesivir |
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| Drug |
placebo IV infusion |
|
| Plasma PK parameters are based on sampling over a 21 day period |
| Plasma PK - Galidesivir AUC (Area Under the Concentration vs. Time Curve) | Serial blood samples for PK assessment of plasma galidesivir were collected at the following time points:
AUC0-inf (AUC from time 0 extrapolated to infinite time) and AUC0-t (AUC from time 0 to time t, where "t" = the last quantifiable concentration) for galidesivir was estimated using non compartmental methods with Phoenix® WinNonlin® v8.1 or higher (Certara, Inc.). | Plasma PK parameters are based on sampling over a 21 day period |
| Galidesivir Renal Clearance | Urine was collected from subjects over a 96 hour period per protocol, analyzed for galidesivir concentrations. Urine PK parameters including CLR (renal clearance of unchanged drug cumulatively over all collection intervals or in a specific interval) were estimated in SAS for Windows v9.4 or higher (SAS Institute, Inc.) based on the recorded urine concentrations and volumes. | Urine PK parameters are based on sampling over a 96 hour period. |
| BG002 |
| 10 mg/kg Galidesivir |
Single IV infusion 10 mg/kg galidesivir |
| BG003 | 15 mg/kg Galidesivir | Single IV infusion 15 mg/kg galidesivir |
| BG004 | 20 mg/kg Galidesivir | Single IV infusion 20 mg/kg galidesivir |
| BG005 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
Single IV infusion 5 mg/kg galidesivir
| OG002 | 10 mg/kg Galidesivir | Single IV infusion 10 mg/kg galidesivir |
| OG003 | 15 mg/kg Galidesivir | Single IV infusion 15 mg/kg galidesivir |
| OG004 | 20 mg/kg Galidesivir | Single IV infusion 20 mg/kg galidesivir |
|
|
| Secondary | Plasma PK - Galidesivir Cmax (Maximum Observed Concentration of Drug) | Serial blood samples for PK assessment of plasma galidesivir were collected at the following time points:
Cmax for galidesivir was estimated using non compartmental methods with Phoenix® WinNonlin® v8.1 or higher (Certara, Inc.). | The PK population included subjects for whom at least 1 PK parameter was estimated. The PK population was the primary population for the PK analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Plasma PK parameters are based on sampling over a 21 day period |
|
|
|
|
| Secondary | Plasma PK - Galidesivir AUC (Area Under the Concentration vs. Time Curve) | Serial blood samples for PK assessment of plasma galidesivir were collected at the following time points:
AUC0-inf (AUC from time 0 extrapolated to infinite time) and AUC0-t (AUC from time 0 to time t, where "t" = the last quantifiable concentration) for galidesivir was estimated using non compartmental methods with Phoenix® WinNonlin® v8.1 or higher (Certara, Inc.). | The PK population included subjects for whom at least 1 PK parameter was estimated. The PK population was the primary population for the PK analysis. Only 5 subjects were included in the 20 mg/kg cohort for AUC0-t analysis, as 1 subject was lost to follow-up after discharge from clinic on Day 5. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Plasma PK parameters are based on sampling over a 21 day period |
|
|
|
|
| Secondary | Galidesivir Renal Clearance | Urine was collected from subjects over a 96 hour period per protocol, analyzed for galidesivir concentrations. Urine PK parameters including CLR (renal clearance of unchanged drug cumulatively over all collection intervals or in a specific interval) were estimated in SAS for Windows v9.4 or higher (SAS Institute, Inc.) based on the recorded urine concentrations and volumes. | The PK population included subjects for whom at least 1 PK parameter was estimated. The PK population was the primary population for the PK analysis. There were only 5 subjects in the 20 mg/kg cohort as 1 subject was lost to follow-up after discharge from clinic on Day 5. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/hr | Urine PK parameters are based on sampling over a 96 hour period. |
|
|
|
| 8 |
| 0 |
| 8 |
| 2 |
| 8 |
| EG001 | 5 mg/kg Galidesivir | Single IV infusion 5 mg/kg galidesivir | 0 | 6 | 0 | 6 | 0 | 6 |
| EG002 | 10 mg/kg Galidesivir | Single IV infusion 10 mg/kg galidesivir | 0 | 6 | 1 | 6 | 0 | 6 |
| EG003 | 15 mg/kg Galidesivir | Single IV infusion 15 mg/kg galidesivir | 0 | 6 | 1 | 6 | 4 | 6 |
| EG004 | 20 mg/kg Galidesivir | Single IV infusion 20 mg/kg galidesivir | 0 | 6 | 0 | 6 | 1 | 6 |
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA (21.1) | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Abdominal Distension | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hepatic lesion | Hepatobiliary disorders | MedDRA (21.1) | Systematic Assessment |
|
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
|
| Upper airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
|
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| D018702 |
| Filoviridae Infections |
| D018701 | Mononegavirales Infections |
| D008992 | Monkey Diseases |
| D018419 | Primate Diseases |
| D000820 | Animal Diseases |
|
| AUC0-t |
|
|
| A model with In-transformed dose (dose continuous) as a fixed effect & subject as a random effect was applied to In-transformed AUC0-t. Dose proportionality was assessed by restricted max likelihood using SAS PROC MIXED. The mean slope was estimated from the power model & the corresponding 90% CI calculated. Although there was no formal statistical hypothesis tested for this secondary objective, there was evidence for dose proportionality if the 90% CI of the fixed slope for In-dose contained 1. | Slope | 1.086 | 2-Sided | 90 | 0.952 | 1.219 | Other |