Phase 1, Safety and Bronchopulmonary PK Study in Healthy Volunteers

NCT03691584 | Completed Phase 1

• 1 other identifier: TP-6076-003
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, open-label, randomized, PK and safety study in a maximum of 25 healthy subjects who have provided a bronchoalveolar lavage (BAL) sample.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (5)

• Concentrations of TP-6076 in plasma

  Pharmacokinetics

  Up to 2, 4, 8, or 24 hours after the start of the final TP-6076 iv infusion on Day 4.

• Concentrations of TP-6076 in epithelial lining fluid (ELF)

  Up to 2, 4, 8, or 24 hours after the start of the final TP-6076 iv infusion on Day 4.

• Concentrations of TP-6076 in alveolar macrophages (AMs)

  Up to 2, 4, 8, or 24 hours after the start of the final TP-6076 iv infusion on Day 4.

• maximum observed concentration (Cmax)

  Up to 2, 4, 8, or 24 hours after the start of the final TP-6076 iv infusion on Day 4.

• time to maximum observed concentration (Tmax)

  Up to 2, 4, 8, or 24 hours after the start of the final TP-6076 iv infusion on Day 4.

Secondary Outcomes (1)

• collection of adverse events

  Screening through Day 20 (+/- 5 days)

Study Arms (1)

BAL PK study

EXPERIMENTAL

Bronchoalveolar lavage procedure performed at either 2, 4, 8, or 24 hours after final dose of TP-6076 on Day 4

Drug: TP-6076; Procedure: Bronchoalveolar lavage

Interventions

TP-6076 DRUG

The dose planned to be administered in this study is an iv infusion of 30 mg TP 6076 q24h for 4 consecutive days (starting on Day 1 and ending on Day 4).

BAL PK study

Bronchoalveolar lavage PROCEDURE

Subjects will be randomized to undergo a BAL at a single time point: either 2, 4, 8, or 24 hours after the start of the final TP-6076 iv infusion on Day 4.

Also known as: BAL

BAL PK study

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Status : Healthy subject
• Gender : Male or female
• Age : 18 to 50 years, inclusive, at screening
• Body mass index (BMI) : 18.0 to 30.0 kg/m2, inclusive, at screening
• Weight : 50 to 105 kg, inclusive, at screening
• At screening, females must be non-pregnant and non-lactating, or of non childbearing potential (either surgically sterilized or physiologically incapable of becoming pregnant, or at least 1 year post menopausal \[amenorrhoea duration of 12 consecutive months\]); non-pregnancy will be confirmed for all females by a serum pregnancy test conducted at screening, admission to the CPU, and follow up.
• Post-menopausal females using hormone replacement therapy should be on a stable regimen and be using this since at least 3 months prior to the first study drug administration.
• Female subjects of childbearing potential who have a fertile male sexual partner must agree to use adequate contraception from screening until 90 days after the follow up visit. Adequate contraception will be methods with low user dependency (ie, implanted hormonal contraception, an intrauterine device, an intrauterine hormone releasing system, bilateral tubal occlusion, and/or a sole vasectomised male partner with medical assessment). Also, total abstinence, in accordance with the lifestyle of the subject, is acceptable.
• Male subjects, if not surgically sterilized, must agree to use adequate contraception when engaging in sexual activity with a female of childbearing potential and not to donate sperm from admission to the CPU until 90 days after the follow-up visit. Adequate contraception for the male subject (and his female partner) will be methods with low user dependency (ie, implanted hormonal contraception, an intrauterine device, an intrauterine hormone releasing system, bilateral tubal occlusion, and/or a sole vasectomised male subject with medical assessment). Also, total abstinence, in accordance with the lifestyle of the subject, is acceptable.
• All prescribed medication must have been stopped at least 30 days prior to admission to the CPU. An exception is made for hormonal contraceptives and a stable regimen of hormone replacement therapy, which may be used throughout the study.
• All over-the-counter medication, vitamin preparations and other food supplements, or herbal medications (eg, St. John's Wort) must have been stopped at least 14 days prior to admission to the CPU. An exception is made for paracetamol, which is allowed up to admission to the CPU.
• Ability and willingness to abstain from alcohol, methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, energy drinks), and grapefruit (juice) from 48 hours prior to admission to the CPU.
• Good physical and mental health on the basis of medical history, physical examination, clinical laboratory, ECG, and vital signs, as judged by the Investigator.
• Willing to comply with the study procedures.
• Willing and able to sign the ICF.

You may not qualify if:

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• Previous participation in the current study.
• Employee of PRA Health Sciences (PRA), Hammersmith Medicines Research Ltd. (HMR), or Tetraphase Pharmaceuticals, Inc.
• Subjects who may not tolerate a BAL, or cannot undergo a BAL due to the presence of contraindications to a BAL (including abnormal blood coagulation parameters, refractory hypoxemia, reactive airway disease or asthma, unstable angina or acute myocardial infarction in the 6 months prior to the first study drug administration).
• History of any relevant lung disease.
• History of relevant drug (including tetracycline-class antibiotics) and/or food allergies.
• Using tobacco products or electronic cigarettes within 6 months prior to the first study drug administration.
• History of alcohol abuse or drug addiction (including soft drugs like cannabis products) within 2 years prior to the first study drug administration.
• Positive drug and alcohol screen (opiates, methadone, cocaine, amphetamines \[including ecstasy\], cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants, cotinine, and alcohol) at screening and admission to the CPU.
• Average intake of more than 24 units of alcohol per week: 1 unit of alcohol equals approximately 250 mL of beer, 100 mL of wine, or 35 mL of spirits).
• Positive screen for hepatitis B surface antigen (HBsAg), antihepatitis C virus (HCV) antibodies, or antihuman immunodeficiency virus (HIV) 1 and 2 antibodies.
• Participation in a drug study within 60 days prior to the first study drug administration in the current study. Participation in more than 3 other drug studies in the 10 months prior to the first study drug administration in the current study.
• Donation or loss of more than 400 mL of blood within 90 days prior to the first study drug administration. Donation or loss of more than 1.5 liters of blood (for male subjects)/more than 1.0 liters of blood (for female subjects) in the 10 months prior to the first study drug administration in the current study.
• Significant and/or acute illness within 5 days prior to the first study drug administration that may impact safety assessments, in the opinion of the Investigator.
• Unsuitable veins for infusion or blood sampling.

Sponsors & Collaborators

• Tetraphase Pharmaceuticals, Inc: lead
• PRA Health Sciences: collaborator

Study Sites (1)

Hammersmith Medicines Research

London, United Kingdom

Location

MeSH Terms

Interventions

Bronchoalveolar Lavage

Intervention Hierarchy (Ancestors)

Therapeutic Irrigation; Investigative Techniques

Study Officials

• Jeremy Dennison, MD

  Hammersmith Medicines Research

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 27, 2018
• First Posted: October 2, 2018
• Study Start: November 26, 2018
• Primary Completion: June 30, 2019
• Study Completion: December 18, 2019
• Last Updated: December 17, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)