ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Intranasal Octreotide (DP1038) in Healthy Adult Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03031535
Recruitment Status : Completed
First Posted : January 25, 2017
Last Update Posted : May 12, 2017
Sponsor:
Information provided by (Responsible Party):
Dauntless Pharmaceuticals

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).

Condition or disease Intervention/treatment Phase
Healthy Volunteer Study Drug: Intranasal octreotide acetate Drug: Subcutaneous octreotide acetate Diagnostic Test: Growth hormone-releasing hormone Diagnostic Test: Arginine hydrochloride Phase 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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

This study consists of two study parts. In Study Part 1, 12 subject will be randomized into one of four study arms using a 4x4 modified latin square design.

In Study Part 2, subjects will be randomized into one of two arms using a 2x2 crossover design.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : January 2017
Actual Primary Completion Date : March 2017
Actual Study Completion Date : March 2017

Resource links provided by the National Library of Medicine


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 Name: DP1038

Drug: Subcutaneous octreotide acetate
Subcutaneous injectable solution of octreotide acetate
Other Name: 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 Name: DP1038

Drug: Subcutaneous octreotide acetate
Subcutaneous injectable solution of octreotide acetate
Other Name: 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 Name: DP1038

Drug: Subcutaneous octreotide acetate
Subcutaneous injectable solution of octreotide acetate
Other Name: 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 Name: DP1038

Drug: Subcutaneous octreotide acetate
Subcutaneous injectable solution of octreotide acetate
Other Name: 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 Name: DP1038

Drug: Subcutaneous octreotide acetate
Subcutaneous injectable solution of octreotide acetate
Other Name: Sandostatin Injection

Diagnostic Test: Growth hormone-releasing hormone
Part of the well established GHRH/Arginine challenge to detect GH deficiency.
Other Name: GHRH

Diagnostic Test: Arginine hydrochloride
Part of the well established GHRH/Arginine challenge to detect GH deficiency.
Other Name: 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 Name: DP1038

Drug: Subcutaneous octreotide acetate
Subcutaneous injectable solution of octreotide acetate
Other Name: Sandostatin Injection

Diagnostic Test: Growth hormone-releasing hormone
Part of the well established GHRH/Arginine challenge to detect GH deficiency.
Other Name: GHRH

Diagnostic Test: Arginine hydrochloride
Part of the well established GHRH/Arginine challenge to detect GH deficiency.
Other Name: R-Gene 10




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03031535


Locations
United States, Arizona
Celerion, Inc.
Tempe, Arizona, United States, 85283
Sponsors and Collaborators
Dauntless Pharmaceuticals
Investigators
Principal Investigator: Jeffrey Zacher, MD Celerion

Responsible Party: Dauntless Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03031535     History of Changes
Other Study ID Numbers: DP1038-PK-101
First Posted: January 25, 2017    Key Record Dates
Last Update Posted: May 12, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Hormones
Growth Hormone-Releasing Hormone
Octreotide
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Gastrointestinal Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents