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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-000607-16 | EudraCT Number |
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| Name | Class |
|---|---|
| PRA Health Sciences | INDUSTRY |
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This is a single center, open-label, fixed sequence study to investigate the effect of multiple oral dosing of Inarigivir Soproxil and a single oral dose of Midazolam in Healthy Subjects
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A: Midazolam | Experimental | All subjects will receive a single oral dose of 2 mg Midazolam on Day 1 |
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| Treatment B and C: Inarigivir | Experimental | All subjects will receive a single oral dose of 400 mg Inarigivir on Day 3, Day 6-18 |
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| Treatment D: Inarigivir with Midazolam | Experimental | All subjects will receive a single oral dose of 400 mg Inarigivir coa administered with a single oral dose of 2 mg Midazolam on Day 19 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Midazolam | Drug | Midazolam |
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| Measure | Description | Time Frame |
|---|---|---|
| Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (Cmax) | Comparison of Cmax for midazolam between Treatments A and D. | Day 1 Treatment A and Day 19 Treatment D, respectively |
| Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (AUC0-t) | Comparison of AUC0-t for midazolam between Treatments A and D. | Day 1 Treatment A and Day 19 Treatment D, respectively |
| Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (AUC0-inf ) | Comparison of AUC0-inf for midazolam between Treatments A and D. | Day 1 Treatment A and Day 19 Treatment D, respectively |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Clinical Relevant Clinical Laboratory, Vital Signs, 12-lead ECG, or Physical Examination | Safety and tolerability were measured via clinical laboratory evaluations, vital signs, 12-lead ECG, or physical examination | Day -1 to Day 20 and Follow-up (5-9 days post-treatment) |
| PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (AUC) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jeroen van de Wetering | PRA Health Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Medical Center Groningen | Groningen | Netherlands |
Each subject was expected to complete treatment groups A, B, C and D; sequentially.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequential Single, Multi-day & Combo Midazolam and Inarigivir | A: All subjects will receive a single oral dose of 2 mg Midazolam on Day 1 B: All subjects will receive a single oral dose of 400 mg Inarigivir on Day 3 C: All subjects receive oral dose of 400 mg Inarigivir once daily from Day 6 to Day 18 D: All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period A |
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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 | Mar 6, 2018 | Mar 25, 2020 |
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| Inarigivir |
| Drug |
Inarigivir |
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A summary of the main plasma PK parameters for inarigivir, Rp-SB 9000, Sp-SB 9000, and Rp-SB 9000 and Sp-SB 9000 combined after a single oral dose of 400 mg inarigivir on Day 3 (Treatment B) and after the last of 14 consecutive daily oral doses of 400 mg inarigivir from Day 6 to 19 (Treatment D) |
| Day 3 and Day 6 to 19 |
| PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (Cmax) | A summary of the main plasma PK parameters for inarigivir, Rp-SB 9000, Sp-SB 9000, and Rp-SB 9000 and Sp-SB 9000 combined after a single oral dose of 400 mg inarigivir on Day 3 (Treatment B) and after the last of 14 consecutive daily oral doses of 400 mg inarigivir from Day 6 to 19 (Treatment D) | Day 3 and Day 6 to 19 |
| COMPLETED |
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| NOT COMPLETED |
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| Treatment Period B |
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| Treatment Period C |
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| Treatment Period D |
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| ID | Title | Description |
|---|---|---|
| BG000 | Sequential Single, Multi-day & Combo Midazolam and Inarigivir | A: All subjects will receive a single oral dose of 2 mg Midazolam on Day 1 B: All subjects will receive a single oral dose of 400 mg Inarigivir on Day 3 C: All subjects receive oral dose of 400 mg Inarigivir once daily from Day 6 to Day 18 D: All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19 |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean age was 30 years; Individual age ranged between 18 and 46 years | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| BMI | Individual BMI ranged between 19.3 and 30.0 kg/m2 | Mean | Standard Deviation | kg/m^2 |
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| 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 | Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (Cmax) | Comparison of Cmax for midazolam between Treatments A and D. | All subjects who received at least one dose of midazolam and had sufficient concentration-time data to reliably estimate PK parameters | Posted | Mean | Full Range | ng/mL | Day 1 Treatment A and Day 19 Treatment D, respectively |
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| Primary | Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (AUC0-t) | Comparison of AUC0-t for midazolam between Treatments A and D. | This outcome measure was prespecified for treatment groups A and D only. | Posted | Mean | Full Range | h.ng/ml | Day 1 Treatment A and Day 19 Treatment D, respectively |
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| Primary | Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (AUC0-inf ) | Comparison of AUC0-inf for midazolam between Treatments A and D. | This outcome measure was prespecified for treatment groups A and D only. | Posted | Mean | Full Range | h.ng/ml | Day 1 Treatment A and Day 19 Treatment D, respectively |
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| Secondary | Number of Participants With Clinical Relevant Clinical Laboratory, Vital Signs, 12-lead ECG, or Physical Examination | Safety and tolerability were measured via clinical laboratory evaluations, vital signs, 12-lead ECG, or physical examination | All participants analyzed | Posted | Count of Participants | Participants | Day -1 to Day 20 and Follow-up (5-9 days post-treatment) |
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| Secondary | PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (AUC) | A summary of the main plasma PK parameters for inarigivir, Rp-SB 9000, Sp-SB 9000, and Rp-SB 9000 and Sp-SB 9000 combined after a single oral dose of 400 mg inarigivir on Day 3 (Treatment B) and after the last of 14 consecutive daily oral doses of 400 mg inarigivir from Day 6 to 19 (Treatment D) | All subjects in treatment arms B and D who received inarigivir and had sufficient concentration-time data to reliably estimate PK parameters | Posted | Mean | Full Range | h.ng/ml | Day 3 and Day 6 to 19 |
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| Secondary | PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (Cmax) | A summary of the main plasma PK parameters for inarigivir, Rp-SB 9000, Sp-SB 9000, and Rp-SB 9000 and Sp-SB 9000 combined after a single oral dose of 400 mg inarigivir on Day 3 (Treatment B) and after the last of 14 consecutive daily oral doses of 400 mg inarigivir from Day 6 to 19 (Treatment D) | All subjects in treatment arms B and D who received inarigivir and had sufficient concentration-time data to reliably estimate PK parameters | Posted | Mean | Full Range | ng/mL | Day 3 and Day 6 to 19 |
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20 days
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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 | Treatment A: Midazolam | All subjects will receive a single oral dose of 2 mg Midazolam on Day 1 Midazolam: Midazolam | 0 | 17 | 0 | 17 | 4 | 17 |
| EG001 | Treatment B: Inarigivir | B: All subjects will receive a single oral dose of 400 mg Inarigivir on Day 3 Inarigivir: Inarigivir | 0 | 17 | 0 | 17 | 4 | 17 |
| EG002 | Treatment C: Inarigivir | C: All subjects receive oral dose of 400 mg Inarigivir once daily from Day 6 to Day 18 Inarigivir: Inarigivir | 0 | 15 | 0 | 15 | 7 | 17 |
| EG003 | Treatment D: Inarigivir With Midazolam | All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19 Midazolam: Midazolam Inarigivir: Inarigivir | 0 | 15 | 0 | 15 | 2 | 15 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | MedDRA 21.0 | Systematic Assessment |
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| Influenza Like Illness | General disorders | MedDRA 21.0 | Systematic Assessment |
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| Sensation of Foreign Body | General disorders | MedDRA 21.0 | Systematic Assessment |
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| Aphthous Ulcer | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Dry Mouth | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Laryngeal Discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Dry eye | Eye disorders | MedDRA 21.0 | Systematic Assessment |
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| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Affect Lability | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
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| Pollakiuria | Renal and urinary disorders | MedDRA 21.0 | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Skin Fissures | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Don Mitchell, Vice President, Operations & Corporate Development | Spring Bank Pharmaceuticals, Inc. | (508) 689-9737 | dmitchell@springbankpharm.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 2, 2018 | May 4, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D008874 | Midazolam |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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