A Study of the Safety, Tolerability, and Pharmacokinetics of SPR720 in Healthy Volunteers

NCT03796910 | Completed Phase 1 DMC

• 1 other identifier: SPR720-101
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics (PK) following single and multiple ascending dose administration of SPR720 administered orally in healthy volunteers.

Conditions

Healthy Volunteers

Keywords

safety; tolerability; pharmacokinetics; SPR720

Outcome Measures

Primary Outcomes (1)

• Treatment emergent adverse events assessments after single and multiple dose administration at baseline and repeatedly until study completion [Safety and Tolerability]

  Incidence and severity of AEs

  Day 1 through last follow-up visit (5-7 days after last dose)

Secondary Outcomes (16)

• Assessment of Pharmacokinetic Parameter (plasma): Cmax measurement

  From Day 1 pre-dose to 48 hours post last dose

• Assessment of Pharmacokinetic Parameter (plasma): CmaxSS measurement

  From Day 1 pre-dose to 48 hours post last dose

• Assessment of Pharmacokinetic Parameter (plasma): CminSS

  From Day 1 pre-dose to 48 hours post last dose

• Assessment of Pharmacokinetic Parameter (plasma): Ctrough

  From Day 1 pre-dose to 48 hours post last dose

• Assessment of Pharmacokinetic Parameter (plasma): CavSS

  From Day 1 pre-dose to 48 hours post last dose

Study Arms (4)

SPR720 for SAD

EXPERIMENTAL

6 out of 8 subjects per cohort will be randomized to receive SPR720

Drug: SPR720 for SAD

Placebo for SAD

PLACEBO COMPARATOR

2 out of 8 subjects per cohort will be randomized to receive placebo

Drug: Placebo for SAD

SPR720 for MAD

EXPERIMENTAL

6 out of 8 subjects per cohort will be randomized to receive SPR720

Drug: SPR720 for MAD

Placebo for MAD

PLACEBO COMPARATOR

2 out of 8 subjects per cohort will be randomized to receive placebo

Drug: Placebo for MAD

Interventions

SPR720 for SAD DRUG

Healthy subjects meeting eligibility criteria will be sequentially randomized to each dose cohort (up to 8 dose ascending cohorts) to receive either SPR720 or placebo. The study drug (SPR720 or placebo) will be administered as a single dose.

Also known as: SPR720 Oral Capsule

SPR720 for SAD

Placebo for SAD DRUG

Healthy subjects meeting eligibility criteria will be sequentially randomized to each dose cohort (up to 8 dose ascending cohorts) to receive either SPR720 or placebo. The study drug (SPR720 or placebo) will be administered orally as a single dose.

Also known as: Placebo oral Capsule

Placebo for SAD

SPR720 for MAD DRUG

Healthy subjects meeting eligibility criteria will be sequentially randomized to each dose cohort (up to 3 cohorts) to receive either SPR720 or placebo. The study drug (SPR720 or placebo) will be administered orally for a total of 7 (or 14) days of dosing.

Also known as: SPR720 Oral Capsule

SPR720 for MAD

Placebo for MAD DRUG

Healthy subjects meeting eligibility criteria will be sequentially randomized to each dose cohort (up to 3 cohorts) to receive either SPR720 or placebo. The study drug (SPR720 or placebo) will be administered orally for a total of 7 (or 14) days of dosing

Also known as: Placebo Oral Capsule

Placebo for MAD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy adult male or female of non-childbearing potential,18 to 55 or ≥ 65 years of age (inclusive) at the time of screening;
• Body mass index (BMI) ≥ 18.5 and ≤ 32 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive). BMI = body weight (kg) / \[height (m)\]2 (subjects 18 to 55 years of age); Body mass index (BMI) ≥ 18 and ≤ 32 (kg/m2) and weight between 50.0 and 100.0 kg (inclusive). BMI = body weight (kg) / \[height (m)\]2 (subjects 65 years of age and older);
• Medically healthy without clinically significant (CS) abnormalities as assessed by the Principal Investigator (or deputy) based on the following at screening assessments:
• a. Detailed medical history, complete physical examination, vital signs, 12-lead ECG, hematology, blood chemistry and urinalysis laboratory variables;
• Willing and able to provide written informed consent;
• Willing and able to comply with all study assessments and adhere to the protocol schedule;
• If female, must be non-lactating and be of non-childbearing potential;
• If male, must agree to not donate sperm for 90 days after the last dose of study drug and, if engaging in vaginal sexual intercourse with a female partner of childbearing potential, agree to use a condom with spermicide in addition to requesting the female partner use a highly effective method of birth control (e.g. intrauterine device, diaphragm with spermicide, hormonal contraceptives) throughout the duration of the study and for 90 days after the last dose of study drug. This criterion also applies to males who have had a vasectomy.

You may not qualify if:

• History or presence of any clinically significant disease state in any body system, as assessed by the Principal Investigator (or deputy), that may affect the outcome of the study or compromise the safety of the subject;
• Subjects who do not have suitable veins for multiple venipunctures/cannulation as assessed by the Principal Investigator (or deputy) at screening;
• Subjects who are unable to demonstrate the ability to swallow a "dummy" capsule (i.e., an empty gelatin capsule) of the size proposed for administration in a particular cohort/dose level;
• History of any clinically significant acute illness or surgery within the previous three months;
• History of chronic gastritis, gastrointestinal tract disorders, including Clostridium difficile infection; chronic liver or biliary disease;
• History of seizure disorder, except for febrile seizures in childhood;
• Documented history of significant hypersensitivity reaction or anaphylaxis to any medication;
• History of significant allergic disease requiring treatment; allergic rhinitis (hay fever) is allowed unless it has required medication for treatment or prophylaxis within the 14 days prior to randomization;
• Clinically significant screening ECG findings as assessed by the investigator;
• Subject or family history of cardiac arrhythmia, prolonged QT syndrome, Torsades de pointes, unexplained sudden cardiac arrest or syncope, sick sinus syndrome or other clinically relevant cardiac disease;
• Clinically significant abnormalities in vital signs at screening and/or prior to randomization;
• Clinically significant screening laboratory abnormalities;
• History or suspicion of routine or chronic drug or alcohol abuse or dependence within 1 year prior to randomization, and/or positive urine drug testing at screening or check-in (Day -1);
• Reported consumption of alcoholic beverages \> 21 units per week on average (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits); positive alcohol urine test at check in (Day -1);
• Use of tobacco, nicotine, or nicotine replacement products within 30 days prior to randomization or planned use during the study; positive carbon monoxide breath test at check in (Day -1);

Sponsors & Collaborators

• Spero Therapeutics: lead
• Simbec Research: collaborator

Study Sites (1)

Simbec Research, Ltd.

Merthyr Tydfil, Mid Glamorgan, CF48 4DR, United Kingdom

Location

Related Publications (1)

• Talley AK, Thurston A, Moore G, Gupta VK, Satterfield M, Manyak E, Stokes S, Dane A, Melnick D. First-in-Human Evaluation of the Safety, Tolerability, and Pharmacokinetics of SPR720, a Novel Oral Bacterial DNA Gyrase (GyrB) Inhibitor for Mycobacterial Infections. Antimicrob Agents Chemother. 2021 Oct 18;65(11):e0120821. doi: 10.1128/AAC.01208-21. Epub 2021 Sep 7.

  PMID: 34491803 DERIVED

MeSH Terms

Interventions

Sagittal Abdominal Diameter; mycophenolic adenine dinucleotide

Intervention Hierarchy (Ancestors)

Body Size; Body Weights and Measures; Body Constitution; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Anthropometry; Investigative Techniques; Physiological Phenomena

Study Officials

• Annelize Koch, MBChB

  Simbec Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Subjects will be randomized in a 3:1 ratio to receive SPR720 or placebo. The randomization code will produced by Simbec using the PROC PLAN procedure of SAS® version 9.3 or higher. The randomization code will include 2 dose-leaders (1 active:1 placebo) in each cohort who will be randomized prior to the remainder of the cohort. The allocation to SPR720 or placebo will be performed using a block randomization algorithm.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo-controlled, single and multiple ascending dose (SAD and MAD) trial

Study Record Dates

• First Submitted: January 3, 2019
• First Posted: January 8, 2019
• Study Start: December 18, 2018
• Primary Completion: September 24, 2019
• Study Completion: September 24, 2019
• Last Updated: October 28, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)