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| Name | Class |
|---|---|
| CPR Pharma Services Pty Ltd, Australia | INDUSTRY |
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The purpose of this study is to assess the safety and tolerability of single and multiple intravenous doses of SPR741 when administered to healthy adult volunteers.
This Phase 1 First in Human study is designed to assess the safety, tolerability and pharmacokinetics of single and multiple intravenous doses of SPR741 when administered to healthy adult volunteers. This is a double-blind, placebo controlled, ascending dose, multi-cohort trial. A total of ninety-six healthy volunteers will be enrolled in 12 cohorts. The study will be conducted in two phases: a single ascending dose (SAD) phase, followed by a multiple ascending dose (MAD) phase. In SAD, participants will receive one dose of SPR741 or placebo. In MAD, participants will receive multiple doses of SPR741 or placebo for 14 consecutive days. In both parts, sequential cohorts will be exposed to increasing doses of SPR741.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SPR741 | Experimental | SPR741 is a novel chemical entity known as a potentiator that specifically interacts with the outer membrane of Gram-negative bacteria to increase the membrane's permeability. This increase in permeability allows Gram-positive antibiotics to enter and kill the cell. SAD cohorts: Subjects will receive single doses of SPR741 over 60 minute IV infusion. Planned doses to be studied are 5, 15, 50, 100, 200, 400, 600 and 800 mg. MAD cohorts: Subjects will receive SPR741 over 60 minute IV infusion three times a day (TID). Four dose groups will be studied. Doses will be determined by assessing SAD cohort data. |
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| Placebo | Placebo Comparator | The placebo used during this study is normal saline (0.9% sodium chloride for injection). SAD: Subjects will receive single infusions of placebo (0.9% sodium chloride for injection) over 60 minutes. MAD: Subjects will receive TID infusions of placebo over 60 minutes for 14 days |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SPR741 | Drug | SAD: Double-blind dosing will occur in cohorts 1 through 8. Six participants will receive single doses of SPR741. The dose escalation steps may be altered following review of the safety data upon completion of each cohort. MAD: The Safety Management Group will evaluate the safety and tolerability data obtained for the participants in Cohorts 1-5 to determine the appropriate dose level of intravenous q8h dosing of SPR741 to be utilized in the first cohort (Cohort 9) in the MAD. Dosing will commence on the morning of Day 1. Three doses will be administered per day at approximately 8 hours apart. Daily dosing will continue for a total of 14 consecutive days. |
| Measure | Description | Time Frame |
|---|---|---|
| Safety measures: adverse events | The frequency and type of adverse events | SAD: 5 to 7 days MAD: 21 to 23 days |
| Safety measures: clinical laboratory testing | Clinical laboratory testing - change from baseline to end of study visit | SAD: Day -1 to day 7; MAD: Day -1 to day 21 |
| Safety measures: pulse rate | Change from baseline to end of study visit | SAD: Day -1 to day 7; MAD: Day -1 to day 21 |
| Safety measures: EKG | Change from baseline to end of study visit | SAD: 5 to 7 days MAD: 21 to 23 days |
| Safety measures: respiratory rate | Change from baseline to end of study visit | SAD: Day -1 to day 7; MAD: Day -1 to day 21 |
| Safety measures: blood pressure | Change from baseline to end of study visit | SAD: Day -1 to day 7; MAD: Day -1 to day 21 |
| Measure | Description | Time Frame |
|---|---|---|
| Individual SPR741 plasma concentration-time curves will be tabulated for each dose cohort. | • Blood draws for PK: pre-dose (within 10 minutes), 30 minutes following the start of infusion, end of infusion and at 90, 150 minutes, 3, 4, 5, 6 and 8 hours following start of infusion (Day 1 (first dose) and Day 14 (last dose)). Five additional blood draws will be obtained at 10, 12, 24, 36 and 48 hours following the start of infusion of the last dose (morning of Day 14). |
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Inclusion Criteria:
Healthy adult males and/or females (of non-child bearing potential), 18 to 55 years of age (inclusive) at the time of screening;
BMI ≥ 18.5 and ≤ 29.9 (kg/m2) and weight between 62.5 and 100.0 kg (inclusive) for Cohort 1 only and 55.0 and 100.0 kg (inclusive) for all other cohorts;
Medically healthy without clinically significant abnormalities at the screening visit or Day -1, including:
Discussion between the PI and the SMR is encouraged regarding any abnormal laboratory value that is outside of the normal range during the pre-dose period.
Be non-smokers (including tobacco, e-cigarettes or marijuana) for at least 1 month prior to participation in the study;
Willing and able to provide written informed consent;
Be willing and able to comply with all study assessments and adhere to the protocol schedule;
Have suitable venous access for drug administration and blood sampling;
If female, be of non-childbearing potential (e.g. post-menopausal as demonstrated by FSH or surgical sterilization i.e., tubal ligation or hysterectomy). Provision of documentation is not required for female sterilization, verbal confirmation is adequate; • If male, a willingness not to donate sperm and if engaging in sexual intercourse with a female partner who could become pregnant, a willingness to use a condom in addition to having the female partner use a highly effective method of birth control (such as an intrauterine device, diaphragm, oral contraceptives, injectable progesterone, subdermal implants, or a tubal ligation). This criterion applies to males (and/or female partners) who are surgically sterile and must be followed from the time of first study drug administration until 30 days after the final administration of study drug.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nicholas Farinola, MB, BSc, FRACP | CMAX - A division of IDT Australia, Limited | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CMAX - A division of IDT Australia, Limited | Adelaide | South Australia | 5000 | Australia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31262767 | Derived | Eckburg PB, Lister T, Walpole S, Keutzer T, Utley L, Tomayko J, Kopp E, Farinola N, Coleman S. Safety, Tolerability, Pharmacokinetics, and Drug Interaction Potential of SPR741, an Intravenous Potentiator, after Single and Multiple Ascending Doses and When Combined with beta-Lactam Antibiotics in Healthy Subjects. Antimicrob Agents Chemother. 2019 Aug 23;63(9):e00892-19. doi: 10.1128/AAC.00892-19. Print 2019 Sep. |
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| ID | Term |
|---|---|
| C000634255 | SPR741 |
| D012965 | Sodium Chloride |
| D007267 | Injections |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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| Placebo | Drug | 0.9% sodium chloride for injection. SAD: Two participants in each cohort will receive matching placebo. MAD: Two participants in each cohort will receive matching placebo. |
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| Day 1 and Day 14 |
| Geometric means will be calculated for Area Under the Curve (AUC) | Blood draws for PK: pre-dose (within 10 minutes), 30 minutes following the start of infusion, end of infusion and at 90, 150 minutes, 3, 4, 5, 6 and 8 hours following start of infusion (Day 1 (first dose) and Day 14 (last dose)). Five additional blood draws will be obtained at 10, 12, 24, 36 and 48 hours following the start of infusion of the last dose (morning of Day 14). | Day 1 and Day 14 |
| Geometric means will be calculated for Concentration maximum (Cmax) | Blood draws for PK: pre-dose (within 10 minutes), 30 minutes following the start of infusion, end of infusion and at 90, 150 minutes, 3, 4, 5, 6 and 8 hours following start of infusion (Day 1 (first dose) and Day 14 (last dose)). Five additional blood draws will be obtained at 10, 12, 24, 36 and 48 hours following the start of infusion of the last dose (morning of Day 14). | Day 1 and Day 14 |
| Geometric means will be calculated for Area Under the Curve (AUC) Urine | • Urine collection for PK: pre-dose Day 1 sample, total collection over 0-4, 4-8 hours following start of infusion of first dose on Day 1; then total collection over 0-4, 4-8, 8-12, 12-24 and 24-48 hours following start of infusion of the last dose (Day 14). | Day 1 and Day 14 |
| Geometric means will be calculated for Concentration maximum (Cmax) Urine | • Urine collection for PK: pre-dose Day 1 sample, total collection over 0-4, 4-8 hours following start of infusion of first dose on Day 1; then total collection over 0-4, 4-8, 8-12, 12-24 and 24-48 hours following start of infusion of the last dose (Day 14). | Day 1 and Day 14 |
| Mean SPR741 plasma concentration-time curves will be tabulated for each dose cohort. | • Blood draws for PK: pre-dose (within 10 minutes), 30 minutes following the start of infusion, end of infusion and at 90, 150 minutes, 3, 4, 5, 6 and 8 hours following start of infusion (Day 1 (first dose) and Day 14 (last dose)). Five additional blood draws will be obtained at 10, 12, 24, 36 and 48 hours following the start of infusion of the last dose (morning of Day 14). | Day 1 and Day 14 |
| D017670 |
| Sodium Compounds |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |