临床试验/NCT03031535

NCT03031535已完成1 期

A Two-Part, Phase 1, Randomized, Crossover Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intranasal Octreotide (DP1038) Versus Subcutaneous Sandostatin® Injection in Healthy Adult Volunteers

Dauntless Pharmaceuticals1 个研究点分布在 1 个国家目标入组 32 人开始时间: 2017年1月最近更新: 2017年5月12日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方
入组人数: 32
试验地点: 1
主要终点: Percentage of subjects reporting adverse events (AEs)/serious adverse events (SAEs).

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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).

详细描述

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.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Crossover
主要目的: Treatment
盲法: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

入排标准

年龄范围: 18 Years 至 50 Years（Adult）
性别: All
接受健康志愿者: 是

入选标准

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

排除标准

•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.

研究组 & 干预措施

Study Part 1 - Arm 2

Experimental

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.

干预措施: Subcutaneous octreotide acetate (Drug)

Study Part 1 - Arm 1

Experimental

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.

干预措施: Intranasal octreotide acetate (Drug)

Study Part 1 - Arm 1

Experimental

干预措施: Subcutaneous octreotide acetate (Drug)

Study Part 1 - Arm 2

Experimental

干预措施: Intranasal octreotide acetate (Drug)

Study Part 1 - Arm 3

Experimental

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.

干预措施: Intranasal octreotide acetate (Drug)

Study Part 1 - Arm 3

Experimental

干预措施: Subcutaneous octreotide acetate (Drug)

Study Part 1 - Arm 4

Experimental

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.

干预措施: Intranasal octreotide acetate (Drug)

Study Part 1 - Arm 4

Experimental

干预措施: Subcutaneous octreotide acetate (Drug)

Study Part 2 - Arm 1

Experimental

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.

干预措施: Intranasal octreotide acetate (Drug)

Study Part 2 - Arm 1

Experimental

干预措施: Subcutaneous octreotide acetate (Drug)

Study Part 2 - Arm 1

Experimental

干预措施: Growth hormone-releasing hormone (Diagnostic Test)

Study Part 2 - Arm 1

Experimental

干预措施: Arginine hydrochloride (Diagnostic Test)

Study Part 2 - Arm 2

Experimental

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.

干预措施: Intranasal octreotide acetate (Drug)

Study Part 2 - Arm 2

Experimental

干预措施: Subcutaneous octreotide acetate (Drug)

Study Part 2 - Arm 2

Experimental

干预措施: Growth hormone-releasing hormone (Diagnostic Test)

Study Part 2 - Arm 2

Experimental

干预措施: Arginine hydrochloride (Diagnostic Test)

结局指标

主要结局

Percentage of subjects reporting adverse events (AEs)/serious adverse events (SAEs).

时间窗: Both Study Parts: Entire study duration, an average of 1 week.

An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement will be categorized as SAE.

次要结局

Area under the plasma concentration-time curve (AUC)(Part 1 - Days 1, 3, 5, and 7 & Part 2 - Days 3 and 5: Pre-dose, 5 min, 10 min, 20 min, 30 min, 40 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose.)
Maximum plasma concentration (Cmax)(Part 1 - Days 1, 3, 5, and 7 & Part 2 - Days 3 and 5: Pre-dose, 5 min, 10 min, 20 min, 30 min, 40 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose.)
Apparent systemic clearance (CL/F)(Part 1 - Days 1, 3, 5, and 7 & Part 2 - Days 3 and 5: Pre-dose, 5 min, 10 min, 20 min, 30 min, 40 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose.)
Apparent volume of distribution (Vz/F)(Part 1 - Days 1, 3, 5, and 7 & Part 2 - Days 3 and 5: Pre-dose, 5 min, 10 min, 20 min, 30 min, 40 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose.)
Insulin-like growth factor-1 (IGF-1) concentrations over time.(Part 2 only - Days 1, 3, and 5: -60 min, -40 min, -20 min, and -5 min pre-dose and post-arginine infusion completion at 0 min, 20 min, 40 min, 60 min, 80 min, 100 min, 120 min, 140 min, and 160 min, and at 4 and 8 hr.)
Time to maximum plasma concentration (Tmax)(Part 1 - Days 1, 3, 5, and 7 & Part 2 - Days 3 and 5: Pre-dose, 5 min, 10 min, 20 min, 30 min, 40 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose.)
Lagtime (Tlag)(Part 1 - Days 1, 3, 5, and 7 & Part 2 - Days 3 and 5: Pre-dose, 5 min, 10 min, 20 min, 30 min, 40 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose.)
Terminal elimination half-life (t1/2)(Part 1 - Days 1, 3, 5, and 7 & Part 2 - Days 3 and 5: Pre-dose, 5 min, 10 min, 20 min, 30 min, 40 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose.)
Elimination rate constant (lambda z)(Part 1 - Days 1, 3, 5, and 7 & Part 2 - Days 3 and 5: Pre-dose, 5 min, 10 min, 20 min, 30 min, 40 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose.)
Growth hormone (GH) concentrations over time.(Part 2 only - Days 1, 3, and 5: -60 min, -40 min, -20 min, and -5 min pre-dose and post-arginine infusion completion at 0 min, 20 min, 40 min, 60 min, 80 min, 100 min, 120 min, 140 min, and 160 min, and at 4 and 8 hr.)

研究者

发起方

Dauntless Pharmaceuticals

申办方类型

Industry

责任方

Sponsor

研究点 (1)

Loading locations...

相似试验

终止

1 期

Pharmacokinetics, Efficacy and Safety of an Octreotide Implant in Patients With Carcinoid SyndromeCarcinoid Syndrome

NCT00884715Endo Pharmaceuticals10

终止

3 期

High Dose Oxytocin Nasal Spray for Treatment of TinnitusTinnitus

NCT04210310NYU Langone Health33

已完成

1 期

Evaluation of Corfluvec Vaccine for the Prevention of COVID-19 in Healthy VolunteersCOVID-19

NCT05696067Tatyana Zubkova200

已完成

1 期

Pharmacokinetic, Safety, and Tolerability Study of Intranasally Administered Esketamine in Elderly and and Healthy Younger Adult ParticipantsHealthy

NCT02345148Janssen Research & Development, LLC16

终止

2 期

Safety and Efficacy of Intranasal Administration of Niclosamide (UNI91103) in Adults With Asymptomatic or Mild COVID-19Covid19

NCT04932915UNION therapeutics4