A Single Dose Study of Debio 1450 in Healthy Subjects

A Phase 1, Double-blind, Placebo-controlled, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Escalating Oral Doses of Debio 1450 in Healthy Subjects

The sponsor is trying to develop a medicine for infections that are not cured by regular antibiotics. They have an experimental drug called Debio 1450 that may work. They need about 48 healthy adults to volunteer for this study.

This study looks at what the body does to the drug. It measures how the amount of drug in blood and urine changes over time.

From the screening visit through the follow-up visit may be up to 40 days. Volunteers go to the clinic in Baltimore for a screening visit. The study doctor chooses qualified volunteers to participate or serve as alternates. Alternates might not actually complete the study procedures.

The study doctor divides participants into groups of eight. Six receive Debio 1450 and 2 receive Placebo. The drug each participant receives is decided by chance - like flipping a coin.

Eligible volunteers check into the clinic for testing and those chosen to participate remain for a 5-day/ 4-night stay. The clinic serves standard meals, except when fasting is required. Participants must stay at the clinic for the length of the study.

This study is a "dose escalation" study. That means that if no safety concerns come up a new group starts. Each new group of eight participants receives more capsules.

The study product is contained in capsules. Each capsule contains either placebo or 40 mg Debio 1450. After fasting overnight, the first two participants in the group receive their capsules. One gets Debio 1450 and one gets Placebo. If these participants tolerate side effects for 24 hours, the remaining six participants receive their assigned capsules.

The plan is to increase the dose for the next group. The study doctor reviews the measurements collected from each group after three days. He may decide to repeat, increase, or lower the dose or even stop the study. The most any participant receives is 800 mg in 20 capsules.

Study Overview

• Status: Completed
• Conditions: Bacterial Infections
• Intervention / Treatment: Drug: Debio 1450; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Early Phase Clinical Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Is a healthy adult
2. Has met protocol-specified criteria for qualification and use of contraception
3. Is willing and able to remain confined in the study unit for the entire duration of the treatment period and comply with restrictions related to food, drink and medications
4. Has voluntarily consented to participate and provided written informed consent prior to any protocol-specific procedures

Exclusion Criteria:

1. Has screening laboratory values outside protocol-specified limits
2. Has history of a clinically significant allergic drug reaction
3. Has donated a volume of plasma or whole blood within a time frame not allowed per protocol

4. Has historical or current use not allowed per protocol of:

   1. over-the-counter medications
   2. certain foods; dietary, mineral or herbal supplements
   3. licit or illicit drugs (including experimental drugs, caffeine, nicotine and alcohol)

5. Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:

   1. the safety or well-being of the participant or study staff
   2. the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding)
   3. the analysis of results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Debio 1450; Debio 1450 40 mg, capsules, orally, once in the morning under fasted conditions	Drug: Debio 1450; Single sentinel dosing of 40 mg per unit capsules is planned to escalate from 80 mg to 160, 320, 480, 640 and 800 mg, per respective dosing group. Doses may be modified based on review of available safety and pharmacokinetic (PK) data.
Placebo Comparator: Placebo; Placebo 0 mg, matching capsules, orally, once in the morning under fasted conditions	Drug: Placebo; Matching single sentinel dosing of placebo capsules is planned to escalate from 2 capsules to 4, 8, 12, 16 and 20 capsules, per respective dosing group. The number of capsules will match those delivering Debio 1450 for the group, as those doses may be modified based on review of available safety and pharmacokinetic (PK) data.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with at least one treatment emergent adverse event (TEAE)	within 10 days post-dose
Maximum observed plasma concentration (Cmax) of Debio 1450	within 60 hours post-dose
Time of maximum observed plasma concentration (tmax) of Debio 1450	within 60 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration-time curve (AUC) of Debio 1450	Categorical results will include from time zero to 24 hours post-dose (AUC0-24), from time zero to the last measured concentration (AUC0-t), and from time zero extrapolated to infinity (AUC0-∞).	pre-dose, 15, 30 and 60 minutes post-dose, and 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48 and 60 hours post-dose
Percentage of AUC0-∞ that is due to extrapolation beyond the last quantifiable concentration measurement (%AUCex) of Debio 1450		pre-dose, 15, 30 and 60 minutes post-dose, and 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48 and 60 hours post-dose
Elimination half-life (t½) of Debio 1450		pre-dose, 15, 30 and 60 minutes post-dose, and 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48 and 60 hours post-dose
Terminal elimination rate constant (λz) of Debio 1450		pre-dose, 15, 30 and 60 minutes post-dose, and 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48 and 60 hours post-dose
Mean residence time (MRT) of Debio 1450		pre-dose, 15, 30 and 60 minutes post-dose, and 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48 and 60 hours post-dose
Apparent clearance following oral administration (CL/F) of Debio 1450		pre-dose, 15, 30 and 60 minutes post-dose, and 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48 and 60 hours post-dose
Apparent volume of distribution of Debio 1450 during terminal phase (Vz/F)		pre-dose, 15, 30 and 60 minutes post-dose, and 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36, 48 and 60 hours post-dose
Cumulative amount of unchanged Debio 1450 excreted in urine (Ae)		pre-dose and 0-2, 2-6, 6-12, 12-24, 24-48 and 48-60 hours post-dose
Percentage of cumulative amount of unchanged Debio 1450 excreted in urine (Ae%)		pre-dose and 0-2, 2-6, 6-12, 12-24, 24-48 and 48-60 hours post-dose
Renal clearance following oral administration		pre-dose and 0-2, 2-6, 6-12, 12-24, 24-48 and 48-60 hours post-dose
Number of participants with clinically significant change from baseline in vital signs		within 10 days post-dose
Number of participants with clinically significant change from baseline in 12-lead electrocardiogram (ECG) parameters		within 48 hours post-dose
Number of participants with clinically significant change from baseline in clinical laboratory parameters		within 51 hours post-dose

Collaborators and Investigators

• Sponsor: Debiopharm International SA
• Investigators: Principal Investigator: Azra Hussaini, MD, Early Phase Clinical Unit - Baltimore, USA

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: June 10, 2014
• First Submitted That Met QC Criteria: June 11, 2014
• First Posted (Estimate): June 12, 2014

Study Record Updates

• Last Update Posted (Estimate): October 23, 2014
• Last Update Submitted That Met QC Criteria: October 21, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Antibiotic; Antibiotic Resistant Bacterial Infection
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections
• Other Study ID Numbers: Debio 1450-102; 217596 (Other Identifier: CRO)