Study of Intranasal Octreotide (DP1038) in Healthy Adult Volunteers

Dauntless Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteer Study

Treatments: Drug: Subcutaneous octreotide acetate; Diagnostic Test: Arginine hydrochloride; Diagnostic Test: Growth hormone-releasing hormone; Drug: Intranasal octreotide acetate

Study type: Interventional

Funder types: Industry

Identifiers

NCT03031535

DP1038-PK-101

Details and patient eligibility

About

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).

Full 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.

Enrollment: 32 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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32 participants in 6 patient groups

Study Part 1 - Arm 1

Experimental group

Description:

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.

Treatment:

Drug: Intranasal octreotide acetate

Drug: Subcutaneous octreotide acetate

Study Part 1 - Arm 2

Experimental group

Description:

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.

Treatment:

Drug: Intranasal octreotide acetate

Drug: Subcutaneous octreotide acetate

Study Part 1 - Arm 3

Experimental group

Description:

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.

Treatment:

Drug: Intranasal octreotide acetate

Drug: Subcutaneous octreotide acetate

Study Part 1 - Arm 4

Experimental group

Description:

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.

Treatment:

Drug: Intranasal octreotide acetate

Drug: Subcutaneous octreotide acetate

Study Part 2 - Arm 1

Experimental group

Description:

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.

Treatment:

Drug: Intranasal octreotide acetate

Diagnostic Test: Growth hormone-releasing hormone

Diagnostic Test: Arginine hydrochloride

Drug: Subcutaneous octreotide acetate

Study Part 2 - Arm 2

Experimental group

Description:

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.

Treatment:

Drug: Intranasal octreotide acetate

Diagnostic Test: Growth hormone-releasing hormone

Diagnostic Test: Arginine hydrochloride

Drug: Subcutaneous octreotide acetate