Healthy VolunteersPhase 1NCT03022175
A First in Human Study of the Safety and Tolerability of Single and Multiple Doses of SPR741 in Healthy Volunteers
A Phase 1 study testing SPR741 in people with Healthy Volunteers, run by Spero Therapeutics at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- SPR741
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteAustralia
- Study dates
- Dec 2016to Sep 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
Australia1 site
CMAX - A division of IDT Australia, Limited
Adelaide, South Australia, 5000
About this study
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
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.
Read the 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.
- Conditions
- Healthy Volunteers
- Being tested
- SPR741, Placebo
- Keywords
- Safety, Tolerability, Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SPR741Drug
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.
PlaceboDrug
Also called 0.9% sodium chloride for injection
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety measures: adverse events
The frequency and type of adverse events
Measured: 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
Measured: SAD: Day -1 to day 7; MAD: Day -1 to day 21
Safety measures: pulse rate
Change from baseline to end of study visit
Measured: SAD: Day -1 to day 7; MAD: Day -1 to day 21
Safety measures: EKG
Change from baseline to end of study visit
Measured: SAD: 5 to 7 days MAD: 21 to 23 days
Safety measures: respiratory rate
Change from baseline to end of study visit
Measured: SAD: Day -1 to day 7; MAD: Day -1 to day 21
Safety measures: blood pressure
Change from baseline to end of study visit
Measured: 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.
- 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: Day 1 and Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2017 (estimated)
- Study startDec 2016
- Primary completionJul 2017
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spero Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- CPR Pharma Services Pty Ltd, Australia
- Responsible party
- Sponsor
- Investigators
- Nicholas Farinola, MB, BSc, FRACP, Principal investigator, CMAX - A division of IDT Australia, Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03022175
- Sponsor's protocol ID
- SPR741-101s
- Status last verified
- Oct 2017
- First submitted
- 16 Dec 2016
- Last updated
- 5 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 31262767
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03022175
- Acronym / sponsor ID
- SPR741-101s
- Conditions
- Healthy Volunteers
- Keywords
- Safety, Tolerability, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Spero TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- CPR Pharma Services Pty Ltd, Australia
- Study start
- Dec 2016
- Primary completion
- Jul 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 16 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SPR741 | Experimental | Drug: SPR741SPR741 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. |
| Placebo | Placebo comparator | Drug: PlaceboThe 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 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- 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;
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SPR741SAD: 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. | Drug | SPR741 |
| PlaceboAlso: 0.9% sodium chloride for injection0.9% sodium chloride for injection. SAD: Two participants in each cohort will receive matching placebo. MAD: Two participants in each cohort will receive matching placebo. | Drug | Placebo |
Primary outcome
Safety measures: adverse events
Time frame: SAD: 5 to 7 days MAD: 21 to 23 days
The frequency and type of adverse events
Safety measures: clinical laboratory testing
Time frame: SAD: Day -1 to day 7; MAD: Day -1 to day 21
Clinical laboratory testing - change from baseline to end of study visit
Safety measures: pulse rate
Time frame: SAD: Day -1 to day 7; MAD: Day -1 to day 21
Change from baseline to end of study visit
Safety measures: EKG
Time frame: SAD: 5 to 7 days MAD: 21 to 23 days
Change from baseline to end of study visit
Safety measures: respiratory rate
Time frame: SAD: Day -1 to day 7; MAD: Day -1 to day 21
Change from baseline to end of study visit
Safety measures: blood pressure
Time frame: SAD: Day -1 to day 7; MAD: Day -1 to day 21
Change from baseline to end of study visit
6 secondary outcomes
Individual SPR741 plasma concentration-time curves will be tabulated for each dose cohort.
Time frame: Day 1 and Day 14
Geometric means will be calculated for Area Under the Curve (AUC)
Time frame: Day 1 and Day 14
Geometric means will be calculated for Concentration maximum (Cmax)
Time frame: Day 1 and Day 14
Geometric means will be calculated for Area Under the Curve (AUC) Urine
Time frame: Day 1 and Day 14
Geometric means will be calculated for Concentration maximum (Cmax) Urine
Time frame: Day 1 and Day 14
Mean SPR741 plasma concentration-time curves will be tabulated for each dose cohort.
Time frame: Day 1 and Day 14
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2017.
- Derived from this study: PubMed 31262767Eckburg 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicholas Farinola, MB, BSc, FRACP principal investigator
CMAX - A division of IDT Australia, Limited
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SPR741 in people with Healthy Volunteers, run by Spero Therapeutics at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety measures: adverse events (time frame: SAD: 5 to 7 days MAD: 21 to 23 days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03022175, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2017.