Phase 1, first-in-human trial to evaluate the safety, tolerability, and pharmacokinetics of ascending single oral doses of octreotide/ LipOra-Peptide in healthy volunteers

Phase 1

• Conditions: Acromegaly

• Registration Number: DRKS00032263
• Lead Sponsor: niversität Heidelberg vertreten durch das Universitätsklinikum

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-07-14
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Pending
• Sex: All
• Target Recruitment: 95

Inclusion Criteria

Men and women of childbearing potential (WOCBP) who are willing to use a highly effective method of contraception during the treatment and 7 d after the last administration of the investigational medicinal product (IMP), or women of no childbearing potential (WNCBP) [defined as women who underwent surgical sterilization (hysterectomy, bilateral oophorectomy or bilateral tubal ligation) or cessation of menses for 12 or more consecutive months and a follicle stimulating hormone (FSH) test with FSH levels 40 mIU/ml], or individuals who are convincingly sexually abstinent,
- An understanding, ability, and willingness to fully comply with study interventions and restrictions,
- Ability to provide written, personally signed and dated informed consent to participate in the study, in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 and applicable regulations, before completing any study-related interventions.
- Body mass index < 30 kg/m2,
- Willingness to follow the pertinent guidelines for prevention of spreading SARS-CoV2 based on SOPs of the hospital administration of the trial site. This may include a SARS-CoV2 testing and proof of vaccination. These rules may change during the course of the trial.

Exclusion Criteria

At the time of SCR
1. Clinically significant or relevant abnormalities in the medical history, physical examination, and laboratory evaluation as assessed by the investigator,
2. Ongoing or past history of physical or psychiatric illness judged by the investigator as clinically relevant,
3. Pregnancy or breast feeding,
4. Any acute or chronic illness or clinically relevant finding known or expected to modify absorption, distribution, metabolism, or excretion of OTT,
5. Any known history of severe allergic or anaphylactic reactions to drugs or food or any other clinically significant allergies,
6. Any known allergies to OTT or further ingredients of the trial drugs,
7. Clinically relevant findings in any of the following investigations at SCR. Minor deviations of laboratory values from the normal range may be accepted if, in the opinion of the investigator, they have no clinical significance for this trial,
a) Hemoglobin (Hb) < 12 g/dl (males) or < 11 g/dl (females),
b) Creatinine clearance < 60 ml/min (Cockcroft-Gault),
c) Total bilirubin > 1.2 x upper limit of normal (ULN), in case of suspected Gilbert’s disease: total bilirubin = 3 x ULN is acceptable,
d) Alanine aminotransferase (ALT) > 1.1 x ULN,
e) Aspartate aminotransferase (AST) > 1.2 x ULN,
f) Thyroid-stimulating hormone (TSH) not within normal limits,
g) Creatine kinase (CK) not within normal limits (volunteers with CK elevations between = 3 x ULN may be included if troponin T is negative),
8. A positive human immunodeficiency virus (HIV) or hepatitis C (HCV) antibody screen, or positive result for Hepatitis B surface antigen (HBsAg),
9. A positive result in the drug screening test at SCR,
10. Any intake of substances (prescription medication, over-the-counter medicine, or herbal preparations with active ingredients) known to inhibit drug metabolizing enzymes or transport enzymes within a period of less than 5 times the respective elimination half-life (t1/2) with regard to the expected date of first dose of IMP (except hormonal contraception, iodine, and levothyroxine),
11. Any intake of substances (prescription medication, over-the-counter medicine, or herbal preparations with active ingredients) known to induce drug metabolizing enzymes or transport enzymes within a period of 14 d with regard to the expected date of first dose of IMP,
12. Use of another IMP within 30 d prior to receiving the first dose of IMP or active enrolment in another drug or vaccine clinical trial,
13. History of immunization within 14 d prior to expected dosing, including SARS-CoV2 vaccinations, and/ or plans to get vaccinated during the observation time.

At day 1, prior to dosing:
14. Any relevant intercurrent illness since SCR,
15. Any intake of substances (prescription medication, over-the-counter medicine, or herbal preparations with active ingredients) known to inhibit drug metabolizing enzymes or transport enzymes within a period of less than 5 times the respective elimination half-life (t1/2) with regard to the expected date of first dose of IMP (except hormonal contraception, iodine, and levothyroxine),
16. Any intake of substances (prescription medication, over-the-counter medicine, or herbal preparations with active ingredients) known to induce drug metabolizing enzymes or transport enzymes within a period of 14 d with regard to the expected date of first dose of IMP, and
17. Ingestion of a meal within the last 10 h (non-fasting state).

Study & Design

• Study Type: interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Part I:<br>Listing, tables, and summaries of all adverse events (AE) and treatment-emerging adverse events (TEAE) by system organ class (SOC), seriousness, relatedness, severity, and outcome.<br><br>Part II:<br>Geometric mean ratio of octreotide´s (OTT) AUC0-8 and Cmax after the following administrations: p.o. with LipOra peptide, p.o. without LipOra peptide, and s.c. at the standard dose of 0.1 mg.