Bioequivalence Study Comparing Two Tablet Formulations of Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) in Healthy Adult Subjects

• Sponsor: Spero Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04421885
• Collaborator: (none)
• Enrollment: 36
• Location: 1
• Arms: 3
• Actual Duration (Months): 1.9
• Patients Per Site Per Month: 18.9

Study Details

Study Description

Brief Summary

A bioequivalence and food-effect study comparing two tablet formulations of tebipenem pivoxil hydrobromide (TBPM-PI-HBr) in healthy adult subjects.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Reference; Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Test	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Open-Label, Randomized, Single-Dose, Semi-Replicate, 4-Period, CrossoverOpen-Label, Randomized, Single-Dose, Semi-Replicate, 4-Period, Crossover
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: An Open-Label, Randomized, Single-Dose, Semi-Replicate, 4-Period, Crossover, Bioequivalence Study Comparing Two Tablet Formulations of Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) in Healthy Adult Subjects
• Actual Study Start Date: Jun 1, 2020
• Actual Primary Completion Date: Jul 11, 2020
• Actual Study Completion Date: Jul 29, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A: TBPM-PI-HBr (Reference - fasted) 600 mg (2 x 300 mg tablets) clinical study drug product batch TBPM-PI-HBr administered at Hour 0 on Day 1, under fasted conditions.	Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Reference; 600 mg (2 x 300 mg tablets) clinical study drug product batch TBPM-PI-HBr.
Experimental: B: TBPM-PI-HBr (Test - fasted) 600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr administered at Hour 0 on Day 1, under fasted conditions.	Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Test; 600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr.
Experimental: C: TBPM-PI-HBr (Test - fed) 600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr administered at Hour 0 on Day 1, under fed conditions.	Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Test; 600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr.

Outcome Measures

Primary Outcome Measures

1. Area under the curve extrapolated to infinity (AUC0-∞). [24h (Day 2) post dose (Arms: A, B, C)]

2. Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (t) (AUC0-t). [24h (Day 2) post dose (Arms: A, B, C)]

3. Maximum plasma concentration (Cmax). [24h (Day 2) post dose (Arms: A, B, C)]

Secondary Outcome Measures

1. Time to the maximum plasma concentration (Tmax). [24h (Day 2) post dose (Arms: A, B, C)]

2. Terminal elimination half-life (t½). [24h (Day 2) post dose (Arms: A, B, C)]

3. Apparent total body clearance (CL/F) [24h (Day 2) post dose (Arms: A, B, C)]

4. Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration (Vz/F). [24h (Day 2) post dose (Arms: A, B, C)]

5. Incidence of treatment-emergent AEs (including SAEs) categorized by severity and relationship to study drug. [12 to 14 days after the last dose of study drug]

   ECG, Clinical Laboratories, Vitals Signs and Physical Exams will be used as a safety measure to detect any AEs.

6. Area under the curve extrapolated to infinity (AUC0-∞). [24h (Day 2) post dose (Arms: B, C)]

   TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.

7. Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (t) (AUC0-t). [24h (Day 2) post dose (Arms: B, C)]

   TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.

8. Maximum plasma concentration (Cmax). [24h (Day 2) post dose (Arms: B, C)]

   TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.

9. Time to the maximum plasma concentration (Tmax). [24h (Day 2) post dose (Arms: B, C)]

   TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.

10. Terminal elimination half-life (t½). [24h (Day 2) post dose (Arms: B, C)]

    TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.

11. Apparent total body clearance (CL/F) [24h (Day 2) post dose (Arms: B, C)]

    TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.

12. Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration (Vz/F). [24h (Day 2) post dose (Arms: B, C)]

    TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy, adult, male or female, 18 to 55 years of age

• Continuous non-smoker.

• Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2.

• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs.

• Has suitable venous access for repeated blood sampling.

• A female of childbearing potential must agree to abstain from sexual activity that could lead to pregnancy.

• A female of non-childbearing potential.

• Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.

Exclusion Criteria:

• Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected to have during the conduct of the study.

• History or presence of clinically significant medical or psychiatric condition or disease.

• History of any illness that might confound the results of the study or poses an additional risk to the subject by their participation in the study.

• History of significant allergic disease requiring treatment.

• History or presence of alcoholism or drug abuse.

• History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds.

• History of known genetic metabolism anomaly associated with carnitine deficiency.

• Female subjects with a positive pregnancy test or who are lactating.

• Positive urine drug or alcohol results.

• Positive results for human immunodeficiency virus (HIV 1 and 2), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).

• QTcF interval is > 460 msec (males) or > 470 msec (females) or has ECG findings deemed abnormal with clinical significance by the PI or designee at the screening visit.

• Estimated creatinine clearance < 80 mL/min at the screening visit.

• Unable to refrain from or anticipates the use of any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical Facility	Tempe	Arizona	United States	85283

Sponsors and Collaborators

• Spero Therapeutics

Investigators

• Study Director: David Melnick, Spero Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Spero Therapeutics
• ClinicalTrials.gov Identifier: NCT04421885
• Other Study ID Numbers: SPR994-105
• First Posted: Jun 9, 2020
• Last Update Posted: Aug 12, 2020
• Last Verified: Aug 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Study Results

No Results Posted as of Aug 12, 2020