Healthy Subjects
Conditions
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.
Detailed description
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. 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). 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. The BAL will be conducted in 5 different subjects at each of the 4 time points, adding up to a total of 20 subjects.
Interventions
DRUGTP-6076
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).
PROCEDUREBronchoalveolar lavage
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.
Sponsors
PRA Health Sciences
Tetraphase Pharmaceuticals, Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* The following inclusion criteria must be met for a subject to be eligible for inclusion in the study: 1. Status : Healthy subject 2. Gender : Male or female 3. Age : 18 to 50 years, inclusive, at screening 4. Body mass index (BMI) : 18.0 to 30.0 kg/m2, inclusive, at screening 5. Weight : 50 to 105 kg, inclusive, at screening 6. 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. 7. 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. 8. 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. 9. 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. 10. 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. 11. 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. 12. 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. 13. Good physical and mental health on the basis of medical history, physical examination, clinical laboratory, ECG, and vital signs, as judged by the Investigator. 14. Willing to comply with the study procedures. 15. Willing and able to sign the ICF.
Exclusion criteria
A subject who meets any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of TP-6076 in plasma | Up to 2, 4, 8, or 24 hours after the start of the final TP-6076 iv infusion on Day 4. | Pharmacokinetics |
| 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
| Measure | Time frame |
|---|---|
| collection of adverse events | Screening through Day 20 (+/- 5 days) |
Countries
United Kingdom
Outcome results
None listed