Study of Intranasal Octreotide (DP1038) in Healthy Adult Volunteers

May 11, 2017 updated by: Dauntless Pharmaceuticals

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tempe, Arizona, United States, 85283
        • Celerion, Inc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 48 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Intranasal octreotide acetate
Intranasal spray of octreotide acetate
Other Names:
  • DP1038
Drug: Subcutaneous octreotide acetate
Subcutaneous injectable solution of octreotide acetate
Other Names:
  • Sandostatin Injection
Experimental: 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.
Drug: Intranasal octreotide acetate
Intranasal spray of octreotide acetate
Other Names:
  • DP1038
Drug: Subcutaneous octreotide acetate
Subcutaneous injectable solution of octreotide acetate
Other Names:
  • Sandostatin Injection
Experimental: 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.
Drug: Intranasal octreotide acetate
Intranasal spray of octreotide acetate
Other Names:
  • DP1038
Drug: Subcutaneous octreotide acetate
Subcutaneous injectable solution of octreotide acetate
Other Names:
  • Sandostatin Injection
Experimental: 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.
Drug: Intranasal octreotide acetate
Intranasal spray of octreotide acetate
Other Names:
  • DP1038
Drug: Subcutaneous octreotide acetate
Subcutaneous injectable solution of octreotide acetate
Other Names:
  • Sandostatin Injection
Experimental: 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.
Drug: Intranasal octreotide acetate
Intranasal spray of octreotide acetate
Other Names:
  • DP1038
Drug: Subcutaneous octreotide acetate
Subcutaneous injectable solution of octreotide acetate
Other Names:
  • Sandostatin Injection
Diagnostic test: Growth hormone-releasing hormone
Part of the well established GHRH/Arginine challenge to detect GH deficiency.
Other Names:
  • GHRH
Diagnostic test: Arginine hydrochloride
Part of the well established GHRH/Arginine challenge to detect GH deficiency.
Other Names:
  • R-Gene 10
Experimental: 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.
Drug: Intranasal octreotide acetate
Intranasal spray of octreotide acetate
Other Names:
  • DP1038
Drug: Subcutaneous octreotide acetate
Subcutaneous injectable solution of octreotide acetate
Other Names:
  • Sandostatin Injection
Diagnostic test: Growth hormone-releasing hormone
Part of the well established GHRH/Arginine challenge to detect GH deficiency.
Other Names:
  • GHRH
Diagnostic test: Arginine hydrochloride
Part of the well established GHRH/Arginine challenge to detect GH deficiency.
Other Names:
  • R-Gene 10

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of subjects reporting adverse events (AEs)/serious adverse events (SAEs).
Time Frame: 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.
Both Study Parts: Entire study duration, an average of 1 week.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the plasma concentration-time curve (AUC)
Time Frame: 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.
AUC from pre-dose to time 't' (AUC[0-t]) and pre-dose to infinite time (AUC[0-infinity]) of intranasal DP1038 versus subcutaneous Sandostatin Injection.
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)
Time Frame: 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 octreotide plasma concentration (Cmax) of intranasal DP1038 versus subcutaneous Sandostatin Injection.
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.
Time to maximum plasma concentration (Tmax)
Time Frame: 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.
Time to maximum octreotide plasma concentration (Tmax) of intranasal DP1038 versus subcutaneous Sandostatin Injection.
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)
Time Frame: 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.
Tlag is the amount of time required to obtain the first measurable concentration of plasma octreotide.
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)
Time Frame: 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.
Plasma decay half-life is the time measured for the octreotide plasma concentration to decrease by one half.
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)
Time Frame: 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.
CL/F is the volume of plasma cleared of octreotide per unit time.
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)
Time Frame: 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.
Lambda z is a quantitative measure of the rate at which octreotide is removed from the body.
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)
Time Frame: 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.
Vz/F is the apparent volume of distribution of octreotide during the terminal elimination phase not corrected for bioavailability.
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.
Time Frame: 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.
GH levels will be collected over time to compare the suppressive ability of intranasal octreotide (DP1038) versus subcutaneous octreotide (Sandostatin Injection) compared to no octreotide on the GH levels after a GHRH/arginine challenge.
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.
Insulin-like growth factor-1 (IGF-1) concentrations over time.
Time Frame: 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.
IGF-1 levels will be collected over time to compare the suppressive ability of intranasal octreotide (DP1038) versus subcutaneous octreotide (Sandostatin Injection) compared to no octreotide on IGF-1 levels after a GHRH/arginine challenge.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dauntless Pharmaceuticals

Investigators

  • Principal Investigator: Jeffrey Zacher, MD, Celerion

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2017

Primary Completion (Actual)

March 1, 2017

Study Completion (Actual)

March 1, 2017

Study Registration Dates

First Submitted

January 17, 2017

First Submitted That Met QC Criteria

January 24, 2017

First Posted (Estimate)

January 25, 2017

Study Record Updates

Last Update Posted (Actual)

May 12, 2017

Last Update Submitted That Met QC Criteria

May 11, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DP1038-PK-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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