Intra-anal Oxymetazoline in Healthy Adult Volunteers

NCT03529487 | Unknown Phase 1 FDA Drug

• 1 other identifier: RDD 121
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, open-label, repeat dose, ascending dose study assessing the PK, safety, tolerability, PD, and dose- or exposure-response of Topical Oxymetazoline for intra-anal application. A total of 32 healthy male and female subjects will be enrolled to receive either Topical Oxymetazoline 1 mg (Cohort A, n=16), 5 mg (Cohort B, n=8) and 10 mg (Cohort C, n=8) applied intra-anally daily (QD) for 11 consecutive days.

Conditions

Fecal Incontinence

Outcome Measures

Primary Outcomes (4)

• Cmax

  Oxymetazoline Maximum observed plasma concentration

  11 days

• Tmax

  Time to maximum concentration (Oxymetazoline), obtained directly from the observed concentration versus time data

  11 days

• AUClast

  Oxymetazoline Area under the plasma concentration-time curve from time 0 to time of last measureable plasma concentration

  11 days

• t½

  Oxymetazoline Terminal elimination half-life

  11 days

Study Arms (1)

Oxymetazoline applied intra analy

EXPERIMENTAL

Drug: Oxymetazoline

Interventions

Oxymetazoline DRUG

Oxymetazoline gel applied intra-analy

Oxymetazoline applied intra analy

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• An Institutional Review Board (IRB) approved informed consent is signed and dated prior to any study-related activities.
• Subject is an adult male or female between the ages of 18 and 60 years, inclusive.
• Female subjects of child-bearing potential must have a negative urine pregnancy test. Females of childbearing potential must practice a highly effective method of pregnancy prevention (defined as \<1% pregnancies per 100 women per year) from one month before screening to one month after the follow-up visit, such as: surgical sterilization, hormonal implant, intrauterine device, or male condom + female diaphragm + vaginal spermicide. Female subject with any of the following circumstances is not required to use a highly effective method of pregnancy prevention: status post-hysterectomy; or, status post-tubal ligation; or, post-menopausal state (defined as \>= 12 months of spontaneous amenorrhea) or \< 12 months of spontaneous amenorrhea with a blood follicle stimulating hormone \> 40 MIU/ml.
• Subject has a body mass index between 18 and 33 kg/m2 (weight/\[height\]2).
• Subject has normal (or abnormal and clinically insignificant) laboratory values at Screening.
• Subject is healthy based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring and have no more than 3 spontaneous bowel movements (SBM) a day or no less than 3 SBMs a week.
• Based on single or averaged QTc values of triplicate ECGs over a brief recording period, QTc \< 450 msec
• Subject has the ability to understand the requirements of the study and a willingness to comply with all study procedures, including retaining a rectal gel for at least 60 min and undergoing repeat rectal manometries lasting 10-15 min.
• Subject has not consumed and agrees to abstain from taking any prescription or non-prescription medications, including herbal and dietary supplements (such as St. John's wort) within 14 days prior to the first dose of study medication (except as authorized by the Investigator and Medical Monitor).
• Subject has not consumed alcohol-containing beverages for 3 days prior to the first scheduled dose and agrees not to consume alcohol through the last study visit.
• Subject has not used tobacco- and nicotine-containing products for 2 months prior to the first scheduled dose and agrees not to use through the last study visit.

You may not qualify if:

• Subject has a hypersensitivity or allergy to oxymetazoline.
• Subject has active or history of cardiovascular or cerebrovascular disease including hypertension, unstable angina, myocardial infarction, transient ischemic attacks/stroke, clinically significant arrhythmia, congestive heart failure, or cardiac valve abnormalities.
• Subject has systolic blood pressure \>130 mm Hg and/or diastolic blood pressure \>80 mm Hg and/or resting heart rate \>90 bpm or resting heart rate \<50 bpm.
• Subject has glaucoma (narrow-angle), Raynaud's disease/phenomenon, thromboangiitis obliterans, scleroderma, and/or Sjögren's syndrome.
• Subject has diabetes per medical history or has fasting plasma glucose level \> 7 mmol/l (126 mg/dl) at screening or has Glycated hemoglobin (HbA1C) ≥ 48 mmol/mol (≥ 6.5 DCCT %) at screening.
• Subject has thyroid problems such as medical history of hypothyroidism, hyperthyroidism, sick euthyroid syndrome, thyroid cancer, thyroid surgery, Radioiodine treatment or enlarged thyroid upon physical examination, or thyroid nodule upon physical examination, or abnormal thyroid-stimulating hormone (TSH) at screening defined as level \>4.0 mIU/mL or level \<0.4 mIU/mL.
• Subject with enlarged prostate as per medical history or per rectal examination in screening.
• Subject has a history of rectal surgery.
• Subject has upon physical examination a rectal deformation or signs of rectal disease such as fissure, hemorrhoids grade 3, rectal prolapse, fistula, infection or space occupying lesion.
• Subjects with a history of or present symptoms related to irritable bowel disease, inflammatory bowel disease, or chronic constipation.
• Subject reporting change in bowel habits in the last 14 days.
• Subject reporting episodes of rectal bleeding in the last 90 days.
• Subjects taking anticoagulants such as Coumarins, Heparins, and Factor Xa inhibitors.
• Subjects taking drugs known to affect rectal tone: nitrates, calcium channel blockers, alpha antagonists, and alpha agonists.
• Subjects taking beta-blockers, and/or cardiac glycosides.

Sponsors & Collaborators

• RDD Pharma Ltd: lead
• United States Department of Defense: collaborator
• Spaulding Clinical Research LLC: collaborator

Study Sites (1)

Spaulding Clinical Research, LLC

West Bend, Wisconsin, 53095, United States

Location

MeSH Terms

Conditions

Fecal Incontinence

Interventions

Oxymetazoline

Condition Hierarchy (Ancestors)

Rectal Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2018
• First Posted: May 18, 2018
• Study Start: August 20, 2018
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: August 2, 2022

Record last verified: 2022-07

Locations

US (1)