A First in Human Study of the Safety and Tolerability of Single and Multiple Doses of SPR741 in Healthy Volunteers

NCT03022175 | Completed Phase 1

• 1 other identifier: SPR741-101s
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Keywords

Safety; Tolerability; Pharmacokinetics

Outcome Measures

Primary Outcomes (6)

• 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

Secondary Outcomes (6)

• Individual SPR741 plasma concentration-time curves will be tabulated for each dose cohort.

  Day 1 and Day 14

• Geometric means will be calculated for Area Under the Curve (AUC)

  Day 1 and Day 14

• Geometric means will be calculated for Concentration maximum (Cmax)

  Day 1 and Day 14

• Geometric means will be calculated for Area Under the Curve (AUC) Urine

  Day 1 and Day 14

• Geometric means will be calculated for Concentration maximum (Cmax) Urine

  Day 1 and Day 14

Study Arms (2)

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.

Drug: SPR741

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

Drug: Placebo

Interventions

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.

SPR741

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.

Also known as: 0.9% sodium chloride for injection

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• Physical examination, vital signs. Vital signs include temperature, heart rate, respiratory rate, and blood pressure;
• Triplicate ECGs without QTcF interval duration greater than 450 msec obtained as an average from the triplicate screening and pre-dose Day 1 ECGs after at least 5 min in a fully supine quiet rest;
• Hemoglobin/hematocrit, white blood cell (WBC) count, and platelet count greater than the lower limit of normal range of the reference laboratory;
• Creatinine, BUN, ALT and AST equal to or less than the upper limit of normal for the reference laboratory; results of all other clinical chemistry and urine analytes without any clinically significant abnormality.
• 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.

You may not qualify if:

• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or surgery within the past three months determined by the PI to be clinically relevant;
• History of known or suspected Clostridium difficile infection;
• Positive urine drug/alcohol testing at screening or check-in (Day -1);
• Positive testing for HIV, HBsAg or HCV;
• History of substance abuse or alcohol abuse (defined as greater than 2 standard drinks on average each and every day, where one standard drink is defined as containing 10 g of alcohol and is equivalent to 1 can or stubby of mid-strength beer, 30 ml nip spirits, or 100 ml wine) within the previous 5 years;
• Use of any prescription medication or any over-the-counter medication, including herbal products and vitamins within 7 days prior to randomization;
• Documented hypersensitivity reaction or anaphylaxis to any medication;
• Donation of blood or plasma within 30 days prior to randomization, or loss of whole blood of more than 500 mL within 30 days prior to randomization, or receipt of a blood transfusion within 1 year of study enrollment;
• Participation in another investigational clinical trial within 30 days prior to Day 1;
• Any other condition or prior therapy, which, in the opinion of the PI, would make the volunteer unsuitable for this study, including unable to cooperate fully with the requirements of the study protocol or likely to be non-compliant with any study requirements.

Sponsors & Collaborators

• Spero Therapeutics: lead
• CPR Pharma Services Pty Ltd, Australia: collaborator

Study Sites (1)

CMAX - A division of IDT Australia, Limited

Adelaide, South Australia, 5000, Australia

Location

Related Publications (1)

• 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.

  PMID: 31262767 DERIVED

MeSH Terms

Interventions

SPR741; Sodium Chloride; Injections

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Nicholas Farinola, MB, BSc, FRACP

  CMAX - A division of IDT Australia, Limited

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2016
• First Posted: January 16, 2017
• Study Start: December 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: September 1, 2017
• Last Updated: October 5, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)