Phase 1 Study of Safety, Tolerability and Pharmacokinetics of SPR994

August 27, 2018 updated by: Spero Therapeutics

A Two-part, Double-blind, Placebo-controlled, Phase I Study of the Safety, Tolerability and Pharmacokinetics of SPR994 Following Single and Multiple Ascending Doses of SPR994 Administered Orally in Healthy Volunteers

This is a double-blind, placebo-controlled, ascending dose, multi-cohort trial. The study will be conducted in 2 parts: a single ascending dose (SAD) part, followed by a multiple ascending dose (MAD) part. In SAD, all subjects will receive 1 dose of SPR994 (100, 300, 600 or 900 mg) or placebo, except for subjects enrolled in food effect cohorts in which subjects will receive one dose following a 10 hour fast and a second dose in the fed state following a minimum 5 days washout period. There is a single, optional, open-label control cohort that may enroll, in which all 8 subjects will receive Orapenem® (tebipenem pivoxil fine granules). In MAD, subjects will receive multiple doses of SPR994 (300 or 600 mg) or placebo for 14 consecutive days at either BID or TID dosing. In both parts, cohorts will be exposed to increasing doses of SPR994 with various extended release formulations.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study is a randomized, double-blind, placebo-controlled, combined single and multiple ascending dose (SAD and MAD) trial. Up to one hundred fifty two (152) subjects aged 18-55, who fulfill the inclusion/exclusion criteria, may be enrolled in this study. Up to a total of 17 SAD and 2 MAD cohorts of eight subjects each will be examined. Subjects in each cohort will be randomized 3:1 to receive SPR994 at doses ranging from 100 mg to 900 mg or placebo in various immediate and timed release formulations. One SAD control cohort, Cohort 12, may be enrolled in which eight subjects will receive a single dose of Orapenem® at 300 mg in a fed and fasted state. Dosing is complete in SAD Cohorts 1-3, 6 and 7. Subjects in Cohorts 1-3 received a single dose of SPR994 and subjects in food effect Cohorts 6 and 7 each received 2 doses. Subjects enrolled in SAD Cohorts 8 and beyond will receive a single dose of SPR994 or placebo in a fasted state and a second dose following a standardized meal to investigate food effect on the pharmacokinetics of SPR994 and TBPM. SAD Cohorts 8 through 10 may run in a staggered or concurrent manner before enrollment of further cohorts. Blinded pharmacokinetic data will be reviewed at the conclusion of Cohort 10 (300 mg fasted & fed). Should the PK be optimized in one of the various time released formulations, the Sponsor may decide to proceed to enrollment of the 600 mg Cohorts using the optimal formulation; other timed release formulations may also be explored at 300 mg dose in a staggered or concurrent manner until an optimal formulation(s) is identified. When an optimal formulation(s) is identified, the 600 mg Cohorts may run in a staggered or concurrent manner. SAD Cohorts 16 (100 mg fasted) and 17 (900 mg fasted) may run prior to or in a staggered or concurrent manner with MAD Cohorts 4 (300 mg) and 5 (600 mg). During the MAD part of the study, subjects will receive 27 doses of SPR994 or placebo over a period of 14 days. Based on the observed PK of SPR994 in prior cohorts, the total number of doses may be increased to 40 doses of SPR994 or placebo administered TID over 14 days; only one dose will be administered on Day 14 to allow for PK sample collection In both SAD and MAD parts of the study, the Cohorts will be exposed to increasing doses of SPR994. Each part (SAD and MAD) of the study will consist of 3 periods: a screening period, a treatment period, and a follow-up period. The safety and tolerability of SPR994 will be assessed based on the types and frequency of adverse events (AEs) reported; concomitant medication usage; and changes from baseline in physical examination, weight, vital signs, ECG, and standard clinical laboratory tests. A Safety Management Group (SMG) will review the data of cohorts prior to escalating to the next dose level.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
124

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Randwick, New South Wales, Australia, 2031
        • Scientia Clinical Research Ltd

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy adult males and/or females (of non-childbearing potential), 18 to 55 years of age (inclusive) at the time of screening;
  • Body mass index ≥ 18.5 and ≤ 29.9 (kg/m2) and 55.0 and 100.0 kg (inclusive) for all cohorts;

  • Medically healthy without clinically significant (CS) abnormalities at the screening visit or Day -1, including:

    1. Physical examination, vital signs including temperature, heart rate, respiratory rate, and blood pressure;
    2. Triplicate electrocardiograms (ECGs) taken at least 1 minute apart with QT wave corrected for heart rate (HR) using Fridericia's method (QTcF) interval duration less than 450 msec obtained as an average from the triplicate screening and pre-dose Day 1 ECGs after at least 5 min in a semi-supine quiet rest;
    3. Haemoglobin > 12.5, haematocrit 37%, white blood cell (WBC) count > 3.5, or platelet count equal to or greater than the lower limit of normal range of the reference laboratory (may be confirmed upon repeat analysis);
    4. Creatinine, blood urea nitrogen (BUN), equal to or less than the upper limit of normal; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) equal to or < 1.5 times the upper limit of normal for the reference laboratory and confirmed on repeat analysis; results of all other clinical chemistry and urine analytes without any CS abnormality.

Discussion between the PI and the Sponsor Medical Monitor 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 blood sampling;
  • If female, be of non-childbearing potential (e.g. post-menopausal as demonstrated by follicle stimulating hormone 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:

  • History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or surgery within the past 3 months determined by the PI to be clinically relevant;
  • History of known or suspected Clostridium difficile infection;
  • History of seizure disorders, except for a single febrile seizure in childhood;
  • Positive urine drug/alcohol testing at screening or Day -1;
  • Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV);
  • History of substance abuse or alcohol abuse (defined as greater than 2 standard drinks on average each and every day, where 1 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: SPR994, FI, F2, F3, F4 Oral Tablets

SPR994 is active against multidrug-resistant Gram-negative and Gram-positive pathogens that cause serious and life-threatening infections, including extended spectrum beta-lactamase (ESBL) producers as well as strains resistant to levofloxacin and trimethoprim/sulfamethoxazole. SPR994 is administered in tablet form orally. Up to five different time released formulations of SPR994 will be studied in this protocol at 100 mg, 300 mg, 600 mg and 900 mg dosages.

SAD Cohorts: One dose (two for food effect cohort) MAD Cohorts: Twenty-seven (27) doses administered twice daily (BID) over a period of 14 days or forty doses administered three times daily (TID) over period of 14 days
Drug: SPR994

SAD: Double-blind dosing will occur in all SAD Cohorts except for Cohort 12. In each cohort, six subjects will receive one of five different timed release formulations of SPR994 and 2 subjects will receive placebo. Subjects in SAD Cohorts 2, 3, 6, 16 and 17 will receive a single dose following a 10-h fast. Subjects in SAD Cohorts 1, 8-15 will receive one dose of SPR994 or placebo following a 10-h fast on Day 1 and a second dose following consumption of a standardized meal on Day 7. The dose escalation steps may be altered following review of the safety data of each cohort.

MAD: Double-blind dosing will occur in all MAD Cohorts. Subjects will receive multiple doses of an optimal timed release formulation of SPR994 in MAD Cohort 4 (300 mg) and Cohort 5 (600 mg) or placebo for 14 consecutive days at either BID or TID dosing beginning on Day 1.

Other Names:
  • SPR994 Oral Tablet
Placebo Comparator: Placebo Oral Tablet

Placebo tablets (100, 300, and 600 mg) are pressed from a single placebo blend consisting of the same inactive ingredients; the active pharmaceutical ingredient (API) is replaced by Mannitol 200SD.

SAD Cohorts: One dose (two for food effect cohort) MAD Cohorts: Twenty-seven (27) doses administered BID over a period of 14 days or forty doses administered TID over a period of 14 days
Drug: Placebo Oral Tablet
Mannitol 200SD SAD: Two subjects in each cohort will receive matching placebo. MAD: Two participants in each cohort will receive matching placebo.
Other Names:
  • Placebo
Other: Optional Orapenem Open-Label Control

A single, optional, open-label, control cohort that may enroll, in which all 8 subjects receive Orapenem.

SAD Cohort: One dose under fasted conditions and one dose under fed conditions.
Drug: Orapenem®
Tebipenem pivoxil granules
Other Names:
  • Orapenem® fine granules

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety measures: adverse events
Time Frame: SAD: 1 to 7 days or 1 to 13 (food effect cohort); MAD 1 to 20 days
The incidence and severity of AEs
SAD: 1 to 7 days or 1 to 13 (food effect cohort); MAD 1 to 20 days
Safety measures: concomitant medications
Time Frame: SAD: 1 to 7 days or 1 to 13 (food effect cohort); MAD: 1 to 20 days
The type and frequency of medications used
SAD: 1 to 7 days or 1 to 13 (food effect cohort); MAD: 1 to 20 days
Safety measures: physical examination
Time Frame: SAD: -1 to 7 days or -1 to 13 (food effect cohort); MAD: -1 to 20 days
Change from baseline to end of study visit
SAD: -1 to 7 days or -1 to 13 (food effect cohort); MAD: -1 to 20 days
Safety measures: weight
Time Frame: SAD: -1 to 7 days or -1 to 13 (food effect cohort); MAD: -1 to 20 days
Change from baseline to end of study visit
SAD: -1 to 7 days or -1 to 13 (food effect cohort); MAD: -1 to 20 days
Safety measures: pulse rate
Time Frame: SAD: -1 to 7 days or -1 to 13 (food effect cohort); MAD: -1 to 20 days
Change from baseline to end of study visit
SAD: -1 to 7 days or -1 to 13 (food effect cohort); MAD: -1 to 20 days
Safety measures: ECG
Time Frame: SAD: -1 to 7 days or -1 to 13 (food effect cohort); MAD: -1 to 20 days
Change from baseline to end of study visit
SAD: -1 to 7 days or -1 to 13 (food effect cohort); MAD: -1 to 20 days
Safety measures: clinical laboratory testing
Time Frame: SAD: -1 to 7 days or -1 to 13 (food effect cohort); MAD: -1 to 20 days
Change from baseline to end of study visit
SAD: -1 to 7 days or -1 to 13 (food effect cohort); MAD: -1 to 20 days
Safety measures: respiratory rate
Time Frame: SAD: -1 to 7 days or -1 to 13 (food effect cohort); MAD: -1 to 20 days
Change from baseline to end of study visit
SAD: -1 to 7 days or -1 to 13 (food effect cohort); MAD: -1 to 20 days
Safety measures: blood pressure
Time Frame: SAD: -1 to 7 days or -1 to 13 (food effect cohort); MAD: -1 to 20 days
Change from baseline to end of study visit
SAD: -1 to 7 days or -1 to 13 (food effect cohort); MAD: -1 to 20 days
Safety measures: body temperature
Time Frame: SAD: -1 to 7 days or -1 to 13 (food effect cohort); MAD: -1 to 20 days
Change from baseline to end of study visit
SAD: -1 to 7 days or -1 to 13 (food effect cohort); MAD: -1 to 20 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pharmacokinetics: Time to maximum concentration (Tmax)
Time Frame: SAD: Day 1 to Day 3 and Day 7 to 9 (Food Effect); MAD Day 1 to 16

Plasma Sample Collection for PK Analysis:

SAD Cohorts 1 and 7: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 2, 3, and 6: Day 1 at the same time-points as SAD Cohorts 1 and 7. SAD Cohorts 8 - 15: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 16 and 17: Day 1 at the same time-points as SAD Cohorts 8 - 15. MAD Cohorts 4 and 5: Day 1 at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12 h following start of the first dose (BID dosing) or pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6 and 8 h following start of first dose and prior to second dose (TID dosing); Prior to the morning dose on Days 2, 3, 5, 7, 9, 11 and 13; Pre-dose, 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8
SAD: Day 1 to Day 3 and Day 7 to 9 (Food Effect); MAD Day 1 to 16
Pharmacokinetics: Maximum concentration (Cmax)
Time Frame: SAD: Day 1 to Day 3 and Day 7 to 9 (Food Effect); MAD Day 1 to 16

Plasma Sample Collection for PK Analysis:

SAD Cohorts 1 and 7: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 2, 3, and 6: Day 1 at the same time-points as SAD Cohorts 1 and 7. SAD Cohorts 8 - 15: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 16 and 17: Day 1 at the same time-points as SAD Cohorts 8 - 15. MAD Cohorts 4 and 5: Day 1 at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12 h following start of the first dose (BID dosing) or pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6 and 8 h following start of first dose and prior to second dose (TID dosing); Prior to the morning dose on Days 2, 3, 5, 7, 9, 11 and 13; Pre-dose, 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8
SAD: Day 1 to Day 3 and Day 7 to 9 (Food Effect); MAD Day 1 to 16
Pharmacokinetics: Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-t)
Time Frame: SAD: Day 1 to Day 3 and Day 7 to 9 (food effect); MAD Day 1 to 16

Plasma Sample Collection for PK Analysis:

SAD Cohorts 1 and 7: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 2, 3, and 6: Day 1 at the same time-points as SAD Cohorts 1 and 7. SAD Cohorts 8 - 15: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 16 and 17: Day 1 at the same time-points as SAD Cohorts 8 - 15. MAD Cohorts 4 and 5: Day 1 at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12 h following start of the first dose (BID dosing) or pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6 and 8 h following start of first dose and prior to second dose (TID dosing); Prior to the morning dose on Days 2, 3, 5, 7, 9, 11 and 13; Pre-dose, 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8
SAD: Day 1 to Day 3 and Day 7 to 9 (food effect); MAD Day 1 to 16
Pharmacokinetics: Area under the concentration-time curve from time 0 to infinity (AUC0-inf)
Time Frame: SAD: Day 1 to Day 3 and Day 7 to 9 (food effect); MAD Day 1 to 16

Plasma Sample Collection for PK Analysis:

SAD Cohorts 1 and 7: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 2, 3, and 6: Day 1 at the same time-points as SAD Cohorts 1 and 7. SAD Cohorts 8 - 15: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 16 and 17: Day 1 at the same time-points as SAD Cohorts 8 - 15. MAD Cohorts 4 and 5: Day 1 at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12 h following start of the first dose (BID dosing) or pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6 and 8 h following start of first dose and prior to second dose (TID dosing); Prior to the morning dose on Days 2, 3, 5, 7, 9, 11 and 13; Pre-dose, 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8
SAD: Day 1 to Day 3 and Day 7 to 9 (food effect); MAD Day 1 to 16
Pharmacokinetics: Terminal Elimination Rate Constant (kel)
Time Frame: SAD: Day 1 to Day 3 and Day 7 to 9 (food effect); MAD Day 1 to 16

Plasma Sample Collection for PK Analysis:

SAD Cohorts 1 and 7: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 2, 3, and 6: Day 1 at the same time-points as SAD Cohorts 1 and 7. SAD Cohorts 8 - 15: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 16 and 17: Day 1 at the same time-points as SAD Cohorts 8 - 15. MAD Cohorts 4 and 5: Day 1 at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12 h following start of the first dose (BID dosing) or pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6 and 8 h following start of first dose and prior to second dose (TID dosing); Prior to the morning dose on Days 2, 3, 5, 7, 9, 11 and 13; Pre-dose, 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8
SAD: Day 1 to Day 3 and Day 7 to 9 (food effect); MAD Day 1 to 16
Pharmacokinetics: Terminal half-life (t1/2)
Time Frame: SAD: Day 1 to Day 3 and Day 7 to 9 (food effect); MAD Day 1 to 16

Plasma Sample Collection for PK Analysis:

SAD Cohorts 1 and 7: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 2, 3, and 6: Day 1 at the same time-points as SAD Cohorts 1 and 7. SAD Cohorts 8 - 15: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 16 and 17: Day 1 at the same time-points as SAD Cohorts 8 - 15. MAD Cohorts 4 and 5: Day 1 at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12 h following start of the first dose (BID dosing) or pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6 and 8 h following start of first dose and prior to second dose (TID dosing); Prior to the morning dose on Days 2, 3, 5, 7, 9, 11 and 13; Pre-dose, 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8
SAD: Day 1 to Day 3 and Day 7 to 9 (food effect); MAD Day 1 to 16
Pharmacokinetics: Terminal clearance (CL/F)
Time Frame: SAD: Day 1 to Day 3 and Day 7 to 9 (food effect); MAD Day 1 to 16

Plasma Sample Collection for PK Analysis:

SAD Cohorts 1 and 7: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 2, 3, and 6: Day 1 at the same time-points as SAD Cohorts 1 and 7. SAD Cohorts 8 - 15: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 16 and 17: Day 1 at the same time-points as SAD Cohorts 8 - 15. MAD Cohorts 4 and 5: Day 1 at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12 h following start of the first dose (BID dosing) or pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6 and 8 h following start of first dose and prior to second dose (TID dosing); Prior to the morning dose on Days 2, 3, 5, 7, 9, 11 and 13; Pre-dose, 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8
SAD: Day 1 to Day 3 and Day 7 to 9 (food effect); MAD Day 1 to 16
Pharmacokinetics: Volume of distribution
Time Frame: SAD: Day 1 to Day 3 and Day 7 to 9 (food effect); MAD Day 1 to 16

Plasma Sample Collection for PK Analysis:

SAD Cohorts 1 and 7: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 2, 3, and 6: Day 1 at the same time-points as SAD Cohorts 1 and 7. SAD Cohorts 8 - 15: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 16 and 17: Day 1 at the same time-points as SAD Cohorts 8 - 15. MAD Cohorts 4 and 5: Day 1 at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12 h following start of the first dose (BID dosing) or pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6 and 8 h following start of first dose and prior to second dose (TID dosing); Prior to the morning dose on Days 2, 3, 5, 7, 9, 11 and 13; Pre-dose, 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8
SAD: Day 1 to Day 3 and Day 7 to 9 (food effect); MAD Day 1 to 16
Pharmacokinetics: Area under the concentration-time curve from 0 to 12 hours from the start of first dose (AUC0-12h)
Time Frame: SAD: Day 1 to Day 3 and Day 7 to 9 (food effect); MAD Day 1 to 16

Plasma Sample Collection for PK Analysis:

SAD Cohorts 1 and 7: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 2, 3, and 6: Day 1 at the same time-points as SAD Cohorts 1 and 7. SAD Cohorts 8 - 15: Days 1 and 7 (Food Effect Cohorts) at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h post-dose.

SAD Cohorts 16 and 17: Day 1 at the same time-points as SAD Cohorts 8 - 15. MAD Cohorts 4 and 5: Day 1 at pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8, 12 h following start of the first dose (BID dosing) or pre-dose and at 15, 30, 45 min and 1, 1.5, 2, 4, 6 and 8 h following start of first dose and prior to second dose (TID dosing); Prior to the morning dose on Days 2, 3, 5, 7, 9, 11 and 13; Pre-dose, 15, 30, 45 min and 1, 1.5, 2, 4, 6, 8
SAD: Day 1 to Day 3 and Day 7 to 9 (food effect); MAD Day 1 to 16
Pharmacokinetics: SPR994 excreted in urine in each collection interval
Time Frame: SAD: Days 1-2 and 7-8 (food effect cohorts). MAD: Day 1-2 and 14-15.

SAD: Urine samples for PK will be collected at pre-dose and during the following intervals(total collection): 0-4, 4-8, 8-12, and 12-24 hours after dosing.

MAD: Urine samples for PK will be collected at pre-dose on Day 1 and during the followingintervals (total collection): 0-4, 4-8, and 8-12 hours after start of first dose (BID dosing) or pre-dose on Day 1 and during the following intervals (total collection): 0-4, 4-8 prior to next dose (Days 1-2); and 0-4, 4-8, 8-12, and 12-24 hours following start of the last dose (Days 14-15).
SAD: Days 1-2 and 7-8 (food effect cohorts). MAD: Day 1-2 and 14-15.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Spero Therapeutics

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
CPR Pharma Services Pty Ltd, Australia

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Charlotte Lemech, FRACP, MD, Scientia Clinical Research Limited

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 20, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 2, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 2, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 19, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 9, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 10, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 28, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 27, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2018

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SPR994-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

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