Study to Assess the Intrapulmonary Pharmacokinetics of SPR859 by Comparing the Plasma, Epithelial Lining Fluid (ELF), and Alveolar Macrophages (AM) Concentrations Following the Oral Administration of Five Doses of SPR994 in Healthy, Nonsmoking Volunteers

NCT04710407 | Completed Phase 1 FDA Drug

• 1 other identifier: SPR994-108
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the intrapulmonary pharmacokinetics (PK), including ELF and AM concentrations, of SPR859 (tebipenem) compared to plasma concentrations of SPR859 (tebipenem) (the active moiety in plasma of the prodrug SPR994) in nonsmoking healthy adult volunteers.

Conditions

Healthy Volunteers

Keywords

pharmacokinetics; TBPM-PI-HBr; tebipenem; alveolar macrophages (AM); epithelial lining fluid (ELF); intrapulmonary

Outcome Measures

Primary Outcomes (2)

• Plasma PK and lung penetration of SPR859 following multiple doses

  Plasma PK parameters will include the area under the curve (AUC) from time zero to the last quantifiable sample (AUC0-t), AUC from time zero to end of dosing interval (AUC0-8). The AUC0-8 values for ELF and AM will be determined. The ratios of the AUC0-8 of ELF to the AUC0-8 of plasma and the AUC0-8 of AM to the AUC0-8 of plasma will be calculated.

  Day 1 to Day 3

• Plasma PK and lung penetration of SPR859 following multiple doses

  Plasma PK parameters will include the maximum concentration (Cmax), minimum concentration (Cmin), time to Cmax (tmax), and the terminal-phase half-life (t1/2).

  Day 1 to Day 3

Secondary Outcomes (4)

• Safety and tolerability, including adverse events (AEs)

  Day 1 to Day 10

• Safety and tolerability, including clinically significant changes from baseline in clinical laboratory values

  Day 1 to Day 10

• Safety and tolerability, including physical examination

  Day 1 to Day 10

• Safety and tolerability, including ECG

  Day 1 to Day 10

Study Arms (1)

TBPM-PI-HBr

EXPERIMENTAL

Healthy subjects meeting eligibility criteria will receive a total of five doses of TBPM-PI-HBr 600 mg orally every 8 hours.

Drug: TBPM-PI-HBr

Interventions

TBPM-PI-HBr DRUG

TBPM-PI-HBr (2 x 300mg tablets) a total of five doses

Also known as: TBPM-PI-HBr oral capsule, SPR994

TBPM-PI-HBr

Eligibility Criteria

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

You may qualify if:

• Adult males or female subjects, between 18 and 55 years of age (both inclusive) at the time of screening
• BMI ≥ 18.5 and ≤ 32 (kg/m2) and weight between 55.0 and 100.0 kg (both inclusive)
• Willing and able to provide written informed consent; Willing and able to comply with all study assessments and adhere to the protocol schedule
• Medically healthy without clinically significant abnormalities as assessed by the Investigator based on screening medical history, physical examination, vital signs, 12-lead ECG, hematology, biochemistry and urinalysis
• Have suitable venous access for blood sampling

You may not qualify if:

• History of seizure disorders
• Positive urine drug, alcohol or cotinine testing at screening or check-in (Day -1)
• Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C antibodies (HCV);
• Positive testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at screening;
• Presence of the following symptoms at screening or within 14 days prior to screening or Check-in (Day -1)
• Fever, chills or sweats (temperature of 38 °C / 100.4 °F or higher)
• Difficulty breathing
• Cough
• Sore throat
• New or recent loss of taste or smell
• Nausea, vomiting or diarrhea;
• Close contact with anyone who tested positive for SARS-CoV-2 infection within 14 days prior to screening or Check-in (Day -1);
• Electrocardiogram (ECG) with QTcF interval duration equal or greater than 450 msec for males and 470 msec for females
• Subjects who have any of the following abnormalities on laboratory values at screening or prior confinement including:
• White blood cell count \< 3,000/mm3, hemoglobin \< 11g/dL;

Sponsors & Collaborators

• Spero Therapeutics: lead
• Clinartis: collaborator

Study Sites (1)

Pulmonary Associates

Phoenix, Arizona, 85032, United States

Location

Related Publications (1)

• Rodvold KA, Gotfried MH, Gupta V, Ek A, Srivastava P, Talley A, Bruss J. Plasma and Intrapulmonary Concentrations of Tebipenem following Oral Administration of Tebipenem Pivoxil Hydrobromide to Healthy Adult Subjects. Antimicrob Agents Chemother. 2022 Jul 19;66(7):e0059022. doi: 10.1128/aac.00590-22. Epub 2022 Jun 28.

  PMID: 35762796 DERIVED

MeSH Terms

Interventions

tebipenem

Study Officials

• David Baratz, MD

  Pulmonary Associates

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2021
• First Posted: January 14, 2021
• Study Start: December 7, 2020
• Primary Completion: March 10, 2021
• Study Completion: March 10, 2021
• Last Updated: March 16, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)