Study Evaluating PK of PTH Administered Orally Via RaniPill™ Capsule

Study Overview
=================
Brief Summary
-----------------
A prospective, single-center, open-label, phase I study evaluating the pharmacokinetics (PK) of human parathyroid hormone (1-34) (PTH) administered via the RaniPill™ capsule (RT-102).

Detailed Description
-----------------
The RaniPill device is a capsule-like ingestible device, which injects a microneedle containing a micro tablet (payload/drug) into the intestinal wall. This is a single-center, prospective, open-label, feasibility study being conducted in two parts. Part 1: Healthy women volunteers, 18-65 years of age, of any race, recruited from the general population and assigned to one of the following groups: RT-102: RT-102 Group 1: 20 µg (N=15) RT-102 Group 2: 80 µg (N=15) Subcutaneous (SC): • SC Group: 20 µg of Forteo (N=10) Part 2: Healthy women, 18-65 years of age, or healthy post-menopausal or surgically sterile with bilateral oophorectomy women of any race, recruited from the general population will have once-a-day repeat dosing with 20 μg dose of RT-102 for 7 days (N= up to 12): Healthy women: N = up to 12 Post-menopausal or surgically sterile volunteers: N = up to 7

Official Title
-----------------
A Phase I Study to Evaluate the Pharmacokinetics of Parathyroid Hormone (1-34) Administered Orally Via RaniPill™ Capsule

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Combination Product: RT-102 (80 μg)
* Drug: Forteo
* Combination Product: RT-102 (20 μg)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Part 1 Participant understands and voluntarily signs the approved informed consent document prior to the performance of any study-specific procedures Willing to comply with all study procedures and available for the entire duration of the study Participant is ambulatory female between 18 to 65 years of age. BMI between 19 to 32 kg/m2. In good health, determined by no clinically significant findings from medical history, physical examination, laboratory tests, and vital signs. Non-menstruating, non-pregnant or non-lactating women during study participation NOTE: Females who are of childbearing potential must have had a negative pregnancy test on day of screening. Contraception (double barrier contraception and be protected by a daily combination birth control pill containing estrogen and progestin or any other form of hormonal contraceptive if cannot use the contraceptive pill) should be used between Screening visit and 30 days after dosing if actively engaged in penile-vaginal intercourse. Part 2: Healthy Women Participant understands and voluntarily signs the approved informed consent document prior to the performance of any study-specific procedures Willing to comply with all study procedures and available for the entire duration of the study Participant is ambulatory female between 18 to 65 years of age. BMI between 19 to 32 kg/m2. In good health, determined by no clinically significant findings from medical history, physical examination, laboratory tests, and vital signs. Non-menstruating, non-pregnant or non-lactating women during study participation NOTE: Females who are of childbearing potential must have had a negative pregnancy test on day of screening. A double barrier approach using highly effective methods of contraception (e.g., oral contraceptives containing combined estrogen and progesterone, a vaginal ring, injectable and implantable hormonal contraceptives, intrauterine hormone-releasing system [e.g., Mirena], progestogen-only hormonal contraception associated with inhibition of ovulation, nonhormonal intrauterine device, bilateral tubal occlusion) should be used between Screening visit and 30 days after dosing if actively engaged in penile-vaginal intercourse. Part 2: Post-menopausal/surgically sterile Participant understands and voluntarily signs the approved informed consent document prior to the performance of any study-specific procedures Willing to comply with all study procedures and available for the entire duration of the study Healthy ambulatory female post-menopausal for at least 1 year or surgically sterile with bilateral oophorectomy BMI between 19 to 32 kg/m2. In good health, determined by no clinically significant findings from medical history, physical examination, laboratory tests, and vital signs. Exclusion Criteria: Part 1 Participants with known history of chronic constipation, gastroparesis / delayed gastric emptying, gastric or duodenal ulcers, dysphagia, dyspepsia, esophagitis, esophageal spasm, GERD, IBD, Crohn's disease, stomas, tumors, ischemic or ulcerative colitis Participant has known history of intolerance of PTH (1-34) Participant has known history of high levels of uric acid outside normal ranges Participant has known history of osteoporosis or other bone disorders (such as Paget's disease) Participant has known history of Cushing's disease, hypo- or hyper-parathyroidism or malabsorptive syndromes within the past year Participant is taking calcium and/or vitamin D supplements within 7 days of treatment (including multi-vitamins containing calcium and/or vitamin D) Participant has febrile illness within 30 days of the study procedures Participant currently treated with parathyroid hormone, parathyroid hormone-related peptide-derived drugs, or bone anabolic steroids, including abaloparatide, teriparatide, or parathyroid hormone (1-84) Participant currently treated with intravenous bisphosphonates for at least 1 month or oral bisphosphonates within the past year (12 months). Subjects who have received a short course of oral bisphosphonate therapy (3 months or less) may be enrolled if the treatment occurred 6 or more months prior to enrollment Participants on a regimen of proton pump inhibitors (e.g. omeprazole) or histamine H2 receptor antagonists (e.g. ranitidine) Participants with known bowel obstruction/stricture/fistula Participants who have undergone gastrointestinal surgery (Roux-en-Y, Billroth II, Whipple, intestinal resection for any reason) Participants who have undergone a recent (less than a month) barium X-ray procedure Participants with known allergies or sensitivity to contrast media or barium sulfate Participant with history of chronic disease that in the investigator's judgement may impact subject safety or study outcomes Participants with congestive heart failure, renal failure Presence of cardiac pacemaker or implanted electromedical device Participant who is pregnant or lactating Participant has received an investigational or marketed drug during a trial within the past 1 month or 5 half-lives of the investigational drug, whichever is longer Participant received COVID-19 vaccine within 7 days of dosing Participant is unlikely, in the investigator's judgment, to be able to complete participation in the study as required per study plan Any other history which, in the investigator's judgment, makes the participant ineligible or places the participant at risk Part 2: Healthy Women Participants with known history of chronic constipation, gastroparesis / delayed gastric emptying, gastric or duodenal ulcers, dysphagia, dyspepsia, esophagitis, esophageal spasm, GERD, IBD, Crohn's disease, stomas, tumors, ischemic or ulcerative colitis Participant has known history of intolerance of PTH (1-34) Participant has known history of high levels of uric acid outside normal ranges Participant has known history of osteoporosis or other bone disorders (such as Paget's disease) Participant has known history of Cushing's disease, hypo- or hyper-parathyroidism or malabsorptive syndromes within the past year Participant is taking calcium and/or vitamin D supplements within 7 days of treatment (including multi-vitamins containing calcium and/or vitamin D) Participant has febrile illness within 30 days of the study procedures Participant currently treated with parathyroid hormone, parathyroid hormone-related peptide-derived drugs, or bone anabolic steroids, including abaloparatide, teriparatide, or parathyroid hormone (1-84) Participant currently treated with intravenous bisphosphonates for at least 1 month or oral bisphosphonates within the past year (12 months). Subjects who have received a short course of oral bisphosphonate therapy (3 months or less) may be enrolled if the treatment occurred 6 or more months prior to enrollment Participants on a higher than the lowest approved therapeutic dose regimen of proton pump inhibitors (see Section 8.3.9 for details) Participants on a H2 receptor antagonists (e.g. ranitidine) Participants with known bowel obstruction/stricture/fistula Participants who have undergone gastrointestinal surgery (Roux-en-Y, Billroth II, Whipple, intestinal resection for any reason) Participants who have undergone a recent (less than a month) barium X-ray procedure Participants with known allergies or sensitivity to contrast media or barium sulfate Participant with history of chronic disease that in the investigator's judgement may impact subject safety or study outcomes Participants with congestive heart failure, renal failure Presence of cardiac pacemaker or implanted electromedical device Participant who is pregnant or lactating Participant has received an investigational or marketed drug during a trial within the past 1 month or 5 half-lives of the investigational drug, whichever is longer Participant received COVID-19 vaccine within 7 days of dosing Participant is unlikely, in the investigator's judgment, to be able to complete participation in the study as required per study plan Any other history which, in the investigator's judgment, makes the participant ineligible or places the participant at risk Part 2: Post-menopausal/surgically sterile Participants with known history of chronic constipation, gastroparesis / delayed gastric emptying, gastric or duodenal ulcers, dysphagia, dyspepsia, esophagitis, esophageal spasm, GERD, IBD, Crohn's disease, stomas, tumors, ischemic or ulcerative colitis Participant has known history of intolerance of PTH (1-34) Participant has known history of high levels of uric acid outside normal ranges Participant has known history of osteoporosis or other bone disorders (such as Paget's disease) Participant has known history of Cushing's disease, hypo- or hyper-parathyroidism or malabsorptive syndromes within the past year Participant is taking calcium and/or vitamin D supplements within 7 days of treatment (including multi-vitamins containing calcium and/or vitamin D) Participant has febrile illness within 30 days of the study procedures Participant currently treated with parathyroid hormone, parathyroid hormone-related peptide-derived drugs, or bone anabolic steroids, including abaloparatide, teriparatide, or parathyroid hormone (1-84) Participant currently treated with intravenous bisphosphonates for at least 1 month or oral bisphosphonates within the past year (12 months). Subjects who have received a short course of oral bisphosphonate therapy (3 months or less) may be enrolled if the treatment occurred 6 or more months prior to enrollment Participants on a higher than the lowest approved therapeutic dose regimen of proton pump inhibitors (see Section 8.3.9 for details) Participants on a H2 receptor antagonists (e.g. ranitidine) Participants with known bowel obstruction/stricture/fistula Participants who have undergone gastrointestinal surgery (Roux-en-Y, Billroth II, Whipple, intestinal resection for any reason) Participants who have undergone a recent (less than a month) barium X-ray procedure Participants with known allergies or sensitivity to contrast media or barium sulfate Participant with history of chronic disease that in the investigator's judgement may impact subject safety or study outcomes Participants with congestive heart failure, renal failure Presence of cardiac pacemaker or implanted electromedical device Participant has received an investigational or marketed drug during a trial within the past 1 month or 5 half-lives of the investigational drug, whichever is longer Participant received COVID-19 vaccine within 7 days of dosing Participant is unlikely, in the investigator's judgment, to be able to complete participation in the study as required per study plan Any other history which, in the investigator's judgment, makes the participant ineligible or places the participant at risk

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RT-102 Group 1<br>In 15 subjects, a RaniPill capsule containing 20 µg of PTH will be administered and serial blood samples will be collected for PK analysis. | Combination Product: RT-102 (20 μg)<br>* RaniPill capsule containing PTH with dose of 20μg<br>|
| Experimental: RT-102 Group 2<br>In 15 subjects, a RaniPill capsule containing 80 µg of PTH will be administered and serial blood samples will be collected for PK analysis. | Combination Product: RT-102 (80 μg)<br>* RaniPill capsule containing PTH with doses of 20 and 80 μg<br>|
| Active Comparator: SC Group<br>In 10 subjects, 20 µg of Forteo will be administered subcutaneously and serial blood samples will be collected for PK analysis. | Drug: Forteo<br>* A commercial formulation of PTH for SC control (20 µg)<br>|
| Experimental: Part 2; Group 1<br>In up to 7 subjects, once-a-day repeat dosing with RT-102 (20 mcg) for 7 days in healthy post-menopausal or surgically sterile with bilateral oophorectomy women. | Combination Product: RT-102 (20 μg)<br>* RaniPill capsule containing PTH with dose of 20μg<br>|
| Experimental: Part 2; Group 2<br>In up to 12 subjects, once-a-day repeat dosing with RT-102 (20 mcg) for 7 days in healthy women. | Combination Product: RT-102 (20 μg)<br>* RaniPill capsule containing PTH with dose of 20μg<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate Cmax of PTH administered via the RaniPill capsule | To obtain PK profiles of single doses of PTH given via RaniPill™ capsule in healthy participants with doses of 20 and 80 μg. Cmax of PTH will be calculated from the PK profiles. | Within 24 hours after ingestion of the device | 
| Evaluate Tmax of PTH administered via the RaniPill capsule | To obtain PK profiles of single doses of PTH given via RaniPill™ capsule in healthy participants with doses of 20 and 80 μg. Tmax of PTH will be calculated from the PK profiles. | Within 24 hours after ingestion of the device | 
| Evaluate AUC of PTH administered via the RaniPill capsule | To obtain PK profiles of single doses of PTH given via RaniPill™ capsule in healthy participants with doses of 20 and 80 μg. Absorption (AUC) of PTH will be calculated from the PK profiles. | Within 24 hours after ingestion of the device | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of RT-102 | Monitoring and recording of adverse events possibly related to RT-102. | Within 24 hours after ingestion of the device | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Healthy Volunteers, Forteo, Parathyroid Hormone, PTH