Study of Intranasal Octreotide (DP1038) in Healthy Adult Volunteers

NCT ID: NCT03031535

Last Updated: 2017-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2017-03-31

Brief Summary

The purpose of the study is to investigate the drug octreotide acetate in a new intranasal formulation and compare it to the FDA-approved subcutaneous (SC) injection formulation. The two octreotide acetate formulations will be evaluated following separate administrations for safety and tolerability including any side effects, the speed at which the drug is absorbed and eliminated in the body, and the ability of the drug to lower the levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1).

Detailed Description

Octreotide is a synthetic octapeptide analog of naturally occurring somatostatin, with similar pharmacological effects but a longer duration of action. It inhibits the pathological secretion of GH from pituitary adenomas, and of serotonin and other hormones by tumors of the gastroenteropancreatic endocrine system. Currently, only injectable octreotide and somatostatin analogs have been approved, for the indications of acromegaly, carcinoid tumors, and vasoactive intestinal peptide tumors.

DP1038, an intranasal formulation of octreotide, is being developed for the treatment of acromegaly, a rare chronic disorder arising from the overproduction of GH, predominantly by pituitary adenomas. Excess GH and associated IGF-1 levels are responsible for multiple symptoms (e.g., headache, tissue swelling, perspiration, joint pain) and significant comorbidities (e.g., diabetes, sleep apnea, cardiovascular abnormalities such as hypertension). In most patients with acromegaly, octreotide consistently normalizes GH and IGF-1 serum concentrations, thereby markedly reducing clinical symptoms.

Conditions

Healthy Volunteer Study

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Study Part 1 - Arm 1

Day 1 - Intranasal octreotide acetate (DP1038) - 400 micrograms; Day 3 - Intranasal octreotide acetate (DP1038) - 1200 micrograms; Day 5 - Intranasal octreotide acetate (DP1038) - 2000 micrograms; Day 7 - Subcutaneous octreotide acetate (Sandostatin Injection) - 100 micrograms.

Group Type: EXPERIMENTAL

Intranasal octreotide acetate

Intervention Type: DRUG

Intranasal spray of octreotide acetate

Subcutaneous octreotide acetate

Intervention Type: DRUG

Subcutaneous injectable solution of octreotide acetate

Study Part 1 - Arm 2

Day 1 - Intranasal octreotide acetate (DP1038) - 1200 micrograms; Day 3 - Intranasal octreotide acetate (DP1038) - 400 micrograms; Day 5 - Subcutaneous octreotide acetate (Sandostatin Injection) - 100 micrograms; Day 7 - Intranasal octreotide acetate (DP1038) - 2000 micrograms.

Group Type: EXPERIMENTAL

Intranasal octreotide acetate

Intervention Type: DRUG

Intranasal spray of octreotide acetate

Subcutaneous octreotide acetate

Intervention Type: DRUG

Subcutaneous injectable solution of octreotide acetate

Study Part 1 - Arm 3

Day 1 - Intranasal octreotide acetate (DP1038) - 2000 micrograms; Day 3 - Subcutaneous octreotide acetate (Sandostatin Injection) - 100 micrograms; Day 5 - Intranasal octreotide acetate (DP1038) - 400 micrograms; Day 7 - Intranasal octreotide acetate (DP1038) - 1200 micrograms.

Group Type: EXPERIMENTAL

Intranasal octreotide acetate

Intervention Type: DRUG

Intranasal spray of octreotide acetate

Subcutaneous octreotide acetate

Intervention Type: DRUG

Subcutaneous injectable solution of octreotide acetate

Study Part 1 - Arm 4

Day 1 - Subcutaneous octreotide acetate (Sandostatin Injection) - 100 micrograms; Day 3 - Intranasal octreotide acetate (DP1038) - 2000 micrograms; Day 5 - Intranasal octreotide acetate (DP1038) - 1200 micrograms; Day 7 - Intranasal octreotide acetate (DP1038) - 400 micrograms.

Group Type: EXPERIMENTAL

Intranasal octreotide acetate

Intervention Type: DRUG

Intranasal spray of octreotide acetate

Subcutaneous octreotide acetate

Intervention Type: DRUG

Subcutaneous injectable solution of octreotide acetate

Study Part 2 - Arm 1

Day 1 - 1 microgram/kilogram of growth hormone-releasing hormone (GHRH) + 30 grams arginine hydrochloride; Day 3 - Intranasal octreotide acetate (DP1038) - dose to be determined from Study Part 1 PK results + 1 microgram/kilogram of GHRH + 30 grams arginine hydrochloride; Day 5 - SC octreotide acetate (Sandostatin Injection) 100 micrograms + 1 microgram/kilogram of GHRH + 30 grams arginine hydrochloride.

Group Type: EXPERIMENTAL

Intranasal octreotide acetate

Intervention Type: DRUG

Intranasal spray of octreotide acetate

Subcutaneous octreotide acetate

Intervention Type: DRUG

Subcutaneous injectable solution of octreotide acetate

Growth hormone-releasing hormone

Intervention Type: DIAGNOSTIC_TEST

Part of the well established GHRH/Arginine challenge to detect GH deficiency.

Arginine hydrochloride

Intervention Type: DIAGNOSTIC_TEST

Part of the well established GHRH/Arginine challenge to detect GH deficiency.

Study Part 2 - Arm 2

Day 1 - 1 microgram/kilogram of GHRH + 30 grams arginine hydrochloride; Day 3 - SC octreotide acetate (Sandostatin Injection) 100 micrograms + 1 microgram/kilogram of GHRH + 30 grams arginine hydrochloride; Day 5 - Intranasal octreotide acetate (DP1038) - dose to be determined from Study Part 1 PK results + 1 microgram/kilogram of GHRH + 30 grams arginine hydrochloride.

Group Type: EXPERIMENTAL

Intranasal octreotide acetate

Intervention Type: DRUG

Intranasal spray of octreotide acetate

Subcutaneous octreotide acetate

Intervention Type: DRUG

Subcutaneous injectable solution of octreotide acetate

Growth hormone-releasing hormone

Intervention Type: DIAGNOSTIC_TEST

Part of the well established GHRH/Arginine challenge to detect GH deficiency.

Arginine hydrochloride

Intervention Type: DIAGNOSTIC_TEST

Part of the well established GHRH/Arginine challenge to detect GH deficiency.

Interventions

Intranasal octreotide acetate

Intranasal spray of octreotide acetate

Intervention Type: DRUG

Subcutaneous octreotide acetate

Subcutaneous injectable solution of octreotide acetate

Intervention Type: DRUG

Growth hormone-releasing hormone

Part of the well established GHRH/Arginine challenge to detect GH deficiency.

Intervention Type: DIAGNOSTIC_TEST

Arginine hydrochloride

Part of the well established GHRH/Arginine challenge to detect GH deficiency.

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

DP1038; Sandostatin Injection; GHRH; R-Gene 10

Eligibility Criteria

Inclusion Criteria

• Body mass index (BMI) 18 and <28 kg/m2 (to minimize variability in SC absorption).
• Be in good general health.

Exclusion Criteria

• Use of any tobacco product within 30 days prior to first dose of study drug.
• Use of any prescription or non-prescription drugs or dietary supplements within 7 days, insulin or hypoglycemic drugs within 3 months, estrogen-containing medication within 3 months, or drugs that may affect GH and IGF-1 levels (e.g., alpha-adrenergic, beta-adrenergic, and cholinergic drugs) within 1 month prior to dosing.
• Subjects will also be excluded if they have a history of gallbladder disease, hypothyroidism, or unexplained hypoglycemia.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Dauntless Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Zacher, MD

Role: PRINCIPAL_INVESTIGATOR

Celerion

Locations

Celerion, Inc.

Tempe, Arizona, United States

Countries

United States

Other Identifiers

DP1038-PK-101

Identifier Type: -

Identifier Source: org_study_id