Clinical trial NCT03022175: A First in Human Study of the Safety and Tolerability of Single and Multiple Doses of SPR741 in Healthy Volunteers
Official title: A Two-part, Double-blind, Placebo-controlled, Phase I Study of the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of SPR741 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Safety
Tolerability
Pharmacokinetics
Lead sponsor: Spero Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: CPR Pharma Services Pty Ltd, Australia
First posted: 2017-01-16
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Healthy adult males and/or females (of non-child bearing potential), 18 to 55 years of age (inclusive) at the time of screening;
2. 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;
3. Medically healthy without clinically significant abnormalities at the screening visit or Day -1, including:

   1. Physical examination, vital signs. Vital signs include temperature, heart rate, respiratory rate, and blood pressure;
   2. 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;
   3. Hemoglobin/hematocrit, white blood cell (WBC) count, and platelet count greater than the lower limit of normal range of the reference laboratory;
   4. 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.
4. Be non-smokers (including tobacco, e-cigarettes or marijuana) for at least 1 month prior to participation in the study;
5. Willing and able to provide written informed consent;
6. Be willing and able to comply with all study assessments and adhere to the protocol schedule;
7. Have suitable venous access for drug administration and blood sampling;
8. 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:

1. 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;
2. History of known or suspected Clostridium difficile infection;
3. Positive urine drug/alcohol testing at screening or check-in (Day -1);
4. Positive testing for HIV, HBsAg or HCV;
5. 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;
6. Use of any prescription medication or any over-the-counter medication, including herbal products and vitamins within 7 days prior to randomization;
7. Documented hypersensitivity reaction or anaphylaxis to any medication;
8. 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;
9. Participation in another investigational clinical trial within 30 days prior to Day 1;
10. 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.

Primary outcomes:
measure: Safety measures: adverse events
timeFrame: SAD: 5 to 7 days MAD: 21 to 23 days
measure: Safety measures: clinical laboratory testing
timeFrame: SAD: Day -1 to day 7; MAD: Day -1 to day 21
measure: Safety measures: pulse rate
timeFrame: SAD: Day -1 to day 7; MAD: Day -1 to day 21
measure: Safety measures: EKG
timeFrame: SAD: 5 to 7 days MAD: 21 to 23 days
measure: Safety measures: respiratory rate
timeFrame: SAD: Day -1 to day 7; MAD: Day -1 to day 21
measure: Safety measures: blood pressure
timeFrame: SAD: Day -1 to day 7; MAD: Day -1 to day 21
Secondary outcomes:
measure: Individual SPR741 plasma concentration-time curves will be tabulated for each dose cohort.
timeFrame: Day 1 and Day 14
measure: Geometric means will be calculated for Area Under the Curve (AUC)
timeFrame: Day 1 and Day 14
measure: Geometric means will be calculated for Concentration maximum (Cmax)
timeFrame: Day 1 and Day 14
measure: Geometric means will be calculated for Area Under the Curve (AUC) Urine
timeFrame: Day 1 and Day 14
measure: Geometric means will be calculated for Concentration maximum (Cmax) Urine
timeFrame: Day 1 and Day 14
measure: Mean SPR741 plasma concentration-time curves will be tabulated for each dose cohort.
timeFrame: Day 1 and Day 14
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: CMAX - A division of IDT Australia, Limited
state: South Australia
Study officials:
affiliation: CMAX - A division of IDT Australia, Limited
name: Nicholas Farinola, MB, BSc, FRACP
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.