A First-in-Human Study of the RaniPill, an Oral Drug Delivery Platform

Study Overview
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Brief Summary
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The objective of this study is to ascertain the safety, tolerability and performance of the RaniPill capsule in healthy volunteers

Detailed Description
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The RaniPill device is capsule-like ingestible device, which injects a microneedle containing a microtablet (payload/drug) into the intestinal wall. This is a phase I (first-in-human) open-label study in healthy volunteers. In 6 subjects, 100 mcg of octreotide (Sandostatin®) will be injected intravenously. Three versions of the RaniPill (A, B and C) will be tested in additional three groups of healthy volunteers (N=20 each). All devices will contain 100 mcg of octreotide. The bioavailability of octreotide will be determined by serial blood sampling in Groups A and B. Performance of the RaniPill will be evaluated in all groups.

Official Title
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A Phase 1 Study of the Safety and Pharmacokinetics of Single Doses of Octreotide Administered Orally Via the RaniPill™ Capsule in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Combination Product: RaniPill capsule containing octreotide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent form Willing to comply with all study procedures and available for the entire duration of the study Age between 18 and 55 years BMI 17 - 32 kg/m2 In good general health confirmed by medical history, physical examination, and absence of clinically important laboratory abnormalities per investigator's judgment; Women of reproductive potential must use, between study day and the final study visit, a highly effective contraceptive, as defined in the Informed Consent Document, and have a negative urine pregnancy test at the time of screening, as well as on the day of study. Exclusion Criteria: Unable to swallow an intact 000 capsule with water History of gastrointestinal surgery or illness, including diarrhea, constipation or other manifestations suggestive of abnormal digestion Use of an antacid, proton pump inhibitor or histamine H2 receptor antagonist within 5 days of study day Barium ingestion within 30 days of study day Allergy or sensitivity to contrast media, iodine, barium sulfate, or latex History chronic disease other than mild to moderate systemic hypertension Menstruation on day of dosing Pregnancy or lactating state Participation in an investigational or marketed drug trial within 30 days of the screening visit Low likelihood, in the investigator's judgment, to complete the study as required per study plan; Any other history which, in the investigator's judgment, makes the subject ineligible or exposes the subject to a risk; History of allergic reactions to a component of the RaniPill device or any allergic history other than common food (i.e. shellfish) or insect (i.e. bees) allergies; Febrile illness within 5 days; History of drug or alcohol abuse or any other factor that, in the investigator's opinion, may interfere with the subject's ability to cooperate and comply with the study procedures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Healthy men and women volunteers
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intravenous octreotide group<br>Octreotide 100 mcg will be injected intravenously and serial blood samples will be collected for PK analysis | Combination Product: RaniPill capsule containing octreotide<br>* Administration of a RaniPill capsule loaded with 100 mcg of octreotide. Serial blood samples will be collected over the following 4 h for pharmacokinetic analysis of octreotide a) injected intravenously and b) delivered directly into the jejunal wall by the RaniPill capsule.<br>|
| Experimental: RaniPill A group<br>In 20 subjects, a RaniPill with a small balloon size will be administered and serial blood samples will be collected for PK analysis | Combination Product: RaniPill capsule containing octreotide<br>* Administration of a RaniPill capsule loaded with 100 mcg of octreotide. Serial blood samples will be collected over the following 4 h for pharmacokinetic analysis of octreotide a) injected intravenously and b) delivered directly into the jejunal wall by the RaniPill capsule.<br>|
| Experimental: RaniPill B group<br>In 20 subjects, a RaniPill with a larger balloon size will be administered and serial blood samples will be collected for PK analysis | Combination Product: RaniPill capsule containing octreotide<br>* Administration of a RaniPill capsule loaded with 100 mcg of octreotide. Serial blood samples will be collected over the following 4 h for pharmacokinetic analysis of octreotide a) injected intravenously and b) delivered directly into the jejunal wall by the RaniPill capsule.<br>|
| Experimental: RaniPill C group<br>In 20 subjects, a RaniPill with a different size will be administered and blood samples will be collected for the presence of drug | Combination Product: RaniPill capsule containing octreotide<br>* Administration of a RaniPill capsule loaded with 100 mcg of octreotide. Serial blood samples will be collected over the following 4 h for pharmacokinetic analysis of octreotide a) injected intravenously and b) delivered directly into the jejunal wall by the RaniPill capsule.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and kind of adverse events possibly related to the RaniPill capsule | All adverse events possibly related to the device, including abdominal pain, nausea and vomiting, injuries to the gastrointestinal tract and abnormal changes in blood tests results will be monitored and recorded | Up to 30 days after ingestion of the device | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile of octreotide delivered by the RaniPill capsule | Measurements of octreotide concentration in plasma samples collected serially over 4 h following the deployment of the RaniPill | 4 to 8 hours | 
| Confirmation of the excretion of all RaniPill device components | Stool examinations to verify that all components of the RaniPill capsule have been defecated | up to 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RaniPill capsule, drug delivery, octreotide, pharmacokinetic