Study of the Safety and Local Tolerability of Intranasal Gel Formulations of XF-73

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01592214
First received: May 3, 2012
Last updated: September 25, 2014
Last verified: September 2014
  Purpose

This is a Phase I, single-center, clinical study of XF-73 to evaluate the local (nasal) safety and tolerability of a modified, thinner lower viscosity formulation of intranasal XF-73 in healthy male and female subjects. In addition, the potential for systemic absorption of XF-73 in the modified, thinner lower viscosity and the previously investigated thicker, higher viscosity formulations and their decolonization efficacy in comparison to placebo will be evaluated. Both parts of the study will be double-blinded and Part 2 will also be placebo-controlled.


Condition Intervention Phase
Staphylococcal Infection
Other: Placebo in 4% Klucel® gel
Drug: XF-73 in 2% Klucel® gel
Drug: XF-73 in 4% Klucel® gel
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Two-Part Phase I Study to Establish and Compare the Safety and Local Tolerability of Two Nasal Formulations of XF-73 for Decolonization of Staphylococcus Aureus: A Previously Investigated 0.5 mg/g Viscosified Gel Formulation Versus a Modified Formulation

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • The local (nasal and nasal passage) and systemic safety and tolerability of XF-73 following nasal administration in healthy male and female subjects via adverse events, physical exams, nasal exams, vital signs, clinical lab tests and electrocardiograms. [ Time Frame: Day 1 through Day 8 (Part 1) and Day 1 through Day 14 (Part 2) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The pharmacokinetics (PK) of XF-73 following nasal administration of two concentrations of a modified formulation (in both parts of the study) and a single concentration of a previously investigated formulation (in Part 2 of the study). [ Time Frame: PK samples will be collected at 0 hr (within 15 min before each dose) and at 15 and 30 min and 1, 2, 4, 8 and 12 hr after each dose. Part 1: Days 1 and 2; Part 2: Days 1 through 6. ] [ Designated as safety issue: No ]
  • The efficacy of the modified formulation of XF-73 and of the previous formulation on nasal load of S. aureus after daily treatment with XF-73 for five days as compared to placebo (in Part 2 of the study only). [ Time Frame: Part 2: Enrollment, Day 1 through Day 6 and Day 14. ] [ Designated as safety issue: No ]

Estimated Enrollment: 56
Study Start Date: August 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Part 2 #4-Placebo in 4% Klucel® gel, concentration 0 mg/g
12 subjects: a placebo in 4% Klucel® gel intranasally to both nares in a volume of 0.3 mL/naris/dose,3 doses 8 hours apart on Day 1 and 2 doses, 12 hours apart on Days 2 to 5. Total daily volume of 1.8 ml on Day 1 and 1.2 ml on Days 2 to 5.
Other: Placebo in 4% Klucel® gel
Placebo: 4% Klucel® gel formulation, concentration 0, total daily volume 1.8 ml, 3 doses 8 hours apart on Day 1 and 1.2 ml, 2 doses 12 hrs apart on Days 2 to 5.
Experimental: Part 1 #1-XF-73 in 2% Klucel® gel, concentration 0.5 mg/g:
4 subjects: 0.5 mg/g concentration of a modified 2% Klucel® gel formulation of XF-73 intranasally to both nares twice in a single day in a volume of 0.3 mL/naris/dose and total daily dose of 0.6 mg.
Drug: XF-73 in 2% Klucel® gel
XF-73 in a modified 2% Klucel® gel formulation: Part 1, #1: concentration 0.5 mg/g, twice a day in volume 0.3 mL/naris/dose, total dose 0.6 mg; Part 1, #2: 2.0 mg/g concentration, twice a day in volume 0.3 mL/naris/dose, total dose 2.4 mg; Part 2, #1: Concentration 0.5 mg/g, 3 doses 8 hours apart on Day 1, total volume 1.8 ml, total dose 0.9 mg, 2 doses 12 hours apart on Days 2-5, total volume 1.2 ml and total dose 0.6 mg ; Part 2, #2: 2.0 mg/g, 3 doses 8 hours apart on Day 1, total volume 1.8 ml, total dose 3.6 mg, 2 doses 12 hours apart on Days 2-5,total volume 1.2 ml and total dose 2.4 mg.
Experimental: Part 1 #2-XF-73 in 2% Klucel® gel, concentration 2.0 mg/g
4 subjects: 2.0 mg/g concentrations of a modified 2% Klucel® gel formulation of XF-73 intranasally to both nares twice in a single day in a volume of 0.3 mL/naris/dose and total daily dose of 2.4 mg.
Drug: XF-73 in 2% Klucel® gel
XF-73 in a modified 2% Klucel® gel formulation: Part 1, #1: concentration 0.5 mg/g, twice a day in volume 0.3 mL/naris/dose, total dose 0.6 mg; Part 1, #2: 2.0 mg/g concentration, twice a day in volume 0.3 mL/naris/dose, total dose 2.4 mg; Part 2, #1: Concentration 0.5 mg/g, 3 doses 8 hours apart on Day 1, total volume 1.8 ml, total dose 0.9 mg, 2 doses 12 hours apart on Days 2-5, total volume 1.2 ml and total dose 0.6 mg ; Part 2, #2: 2.0 mg/g, 3 doses 8 hours apart on Day 1, total volume 1.8 ml, total dose 3.6 mg, 2 doses 12 hours apart on Days 2-5,total volume 1.2 ml and total dose 2.4 mg.
Experimental: Part 2 #1- XF-73 in 2 % Klucel® gel, concentration 0.5 mg/g
12 subjects: a modified 2% Klucel® gel formulation of XF-73 intranasally to both nares in a concentration of 0.5 mg/g and volume of 0.3 mL/naris/dose, 3 doses 8 hours apart on Day 1 and 2 doses, 12 hours apart on Days 2 to 5. Total daily volume of 1.8 ml on Day 1 and 1.2 ml on Days 2 to 5; and total daily dose of 0.9 mg on Day 1 and 0.6 mg on Days 2 to 5.
Drug: XF-73 in 2% Klucel® gel
XF-73 in a modified 2% Klucel® gel formulation: Part 1, #1: concentration 0.5 mg/g, twice a day in volume 0.3 mL/naris/dose, total dose 0.6 mg; Part 1, #2: 2.0 mg/g concentration, twice a day in volume 0.3 mL/naris/dose, total dose 2.4 mg; Part 2, #1: Concentration 0.5 mg/g, 3 doses 8 hours apart on Day 1, total volume 1.8 ml, total dose 0.9 mg, 2 doses 12 hours apart on Days 2-5, total volume 1.2 ml and total dose 0.6 mg ; Part 2, #2: 2.0 mg/g, 3 doses 8 hours apart on Day 1, total volume 1.8 ml, total dose 3.6 mg, 2 doses 12 hours apart on Days 2-5,total volume 1.2 ml and total dose 2.4 mg.
Experimental: Part 2 #2- XF-73 in 2% Klucel® gel, concentration 2.0 mg/g
12 subjects; a modified 2% Klucel® gel formulation of XF-73 intranasally to both nares in a concentration of 2.0 mg/g and volume of 0.3 mL/naris/dose,3 doses 8 hours apart on Day 1 and 2 doses, 12 hours apart on Days 2 to 5. Total daily volume of 1.8 ml on Day 1 and 1.2 ml on Days 2 to 5; and total daily dose of 3.6 mg on Day 1 and 2.4 mg on Days 2 to 5.
Drug: XF-73 in 2% Klucel® gel
XF-73 in a modified 2% Klucel® gel formulation: Part 1, #1: concentration 0.5 mg/g, twice a day in volume 0.3 mL/naris/dose, total dose 0.6 mg; Part 1, #2: 2.0 mg/g concentration, twice a day in volume 0.3 mL/naris/dose, total dose 2.4 mg; Part 2, #1: Concentration 0.5 mg/g, 3 doses 8 hours apart on Day 1, total volume 1.8 ml, total dose 0.9 mg, 2 doses 12 hours apart on Days 2-5, total volume 1.2 ml and total dose 0.6 mg ; Part 2, #2: 2.0 mg/g, 3 doses 8 hours apart on Day 1, total volume 1.8 ml, total dose 3.6 mg, 2 doses 12 hours apart on Days 2-5,total volume 1.2 ml and total dose 2.4 mg.
Active Comparator: Part 2 # 3-XF-73 in 4% Klucel® gel, concentration 0.5 mg/g:
12 subjects: a modified 4% Klucel® gel formulation of XF-73 intranasally to both nares in a concentration of 0.5 mg/g and volume of 0.3 mL/naris/dose in, 3 doses 8 hours apart on Day 1 and 2 doses, 12 hours apart on Days 2 to 5. Total daily volume of 1.8 ml on Day 1 and 1.2 ml on Days 2 to 5; and total daily dose of 0.9 mg on Day 1 and 0.6 mg on Days 2 to 5.
Drug: XF-73 in 4% Klucel® gel
XF-73 in a 4% Klucel® gel formulation: Part 2 #3: concentration of 0.5 mg/g and volume of 0.3 mL/naris/dose in 3 doses 8 hours apart on Day 1 and 2 doses, 12 hours apart on Days 2 to 5. Total daily volume of 1.8 ml on Day 1 and 1.2 ml on Days 2 to 5; and total daily dose of 0.9 mg on Day 1 and 0.6 mg on Days 2 to 5.

Detailed Description:

The proposed Phase I study will be conducted in two distinct parts. Study subjects will be healthy volunteers, male or female, aged 18 - 45 years. In Part 2 subjects will also need to be confirmed as persistent nasal SA carriers (n = 48). Persistence will be confirmed from 2 pre-trial nasal swabs and final swab just prior to first dosing event. Part 1; this will involve assessment of safety, local tolerability and pharmacokinetics (PK) of the modified formulation (n=4 for each XF-73 concentration). Subjects will receive intranasal applications of 5,15-bis-[4-(3-Trimethylammonio-propyloxy)-phenyl]-porphyrin dichloride (XF-73), administration will last one day, i.e. two applications per naris. Part 2; this will be a comparison of 2 XF-73 concentrations (0.5 & 2.0 mg/g) of the thinner lower viscosity formulation with the existing viscosified, preserved formulation at 0.5 mg/g. Subjects will be confirmed as persistent nasal SA carriers as assessments will include evaluation of staphylococcal colonization to enable comparison of the new and existing clinical formulations (n = 12 x 3). Administration will last five days, being three times a day on Day 1, then twice a day thereafter. Subjects will undergo body decontamination with chlorhexidine in order to isolate the effect upon the nares and remove this potential confounding factor. A placebo group (n=12) will be included to assess the effect of body decontamination.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Normal, healthy male or female subjects aged between 18 and 45 years inclusive.
  • For Part 2 only: Normal healthy subjects confirmed to be persistent SA carriers (NOTE: Persistent SA carriage is defined by 3 separate, SA (Staphylococcus aureus) positive cultures from nasal swabs: the first taken at pre-Screening no more than 12 weeks (84 days) prior to first dosing, a confirmatory swab taken at Screening at least 7 days after pre-Screening and a final confirmation swab taken on Admission, a day before dosing and at least 7 days after screening. Subjects may be dosed with only two positive swabs while awaiting the result of the third swab obtained on Admission, but dosing will be discontinued in subjects whose Admission swab is found to be negative for SA.
  • Subject must be healthy, in the opinion of the Investigator, as determined by medical history (MH), physical examination (PE), normal nasal examination, and vital signs (VS).
  • Subject's 12-lead electrocardiogram (ECG) must be normal or abnormal not clinically significant as reported by the overreading cardiologist.
  • Subject's clinical laboratory results at Screening must be acceptable (within normal range or within expanded range, if present as described in Appendix D). Subjects may undergo one repeat screening test of an out-of-range analyte at the discretion of the investigator to confirm a plausible alternative explanation that will be indicated in the source documentation.
  • Subjects with non-clinically significant laboratory values outside the reference range (or expanded range if present) in Appendix D which do not meet withdrawal criteria or halting rules (Section 5.4 and 8.6, respectively) at Day -1 may be eligible for enrollment at the discretion of the investigator. Subjects may undergo one repeat screening test of the out-of-range analyte at the discretion of the investigator to confirm a plausible alternative explanation. Abnormal urine dipstick values for blood/hemoglobin, nitrite, and leukocyte esterase will not be exclusionary if a microscopic examination of the urine on the same sample or the most recent sample obtained prior to dosing is normal for blood and leukocytes. Abnormal laboratory values at Screening or Day -1 will be assigned a toxicity grade (Appendix D).
  • Subjects who are able and willing to provide written informed consent to participate in the study.
  • Subject agrees to comply with all study requirements.
  • All female subjects of childbearing potential must have a negative serum and urine pregnancy test at Screening and Admission respectively.
  • Subjects who have a body mass index (BMI) >/= 18.5 kg/m^2 and </= 35 kg/m^2.
  • Subject agrees not to participate in another clinical trial at any time during the study period.

Exclusion Criteria:

  • Female subjects who are pregnant or who are lactating.
  • Heterosexually active females of child-bearing potential, defined as being physiologically capable of becoming pregnant, unless they agree to use two of the following acceptable methods of contraception throughout their participation in the study and for at least 12 weeks after the final dose: (a) established use of oral, injected or implanted hormonal contraception, (b) intrauterine Device (IUD or Coil), (c) a female barrier method (diaphragm or cervical/vault cap) and/or (d) condom plus spermicidal cream/gel. Women who are not sexually active (abstinent) but become active must use two of the listed contraceptive methods.
  • Heterosexually active males unless they agree to use two concomitant acceptable methods of contraception throughout their participation in the study and for at least 12 weeks after receiving their final dose of study medication (examples include: vasectomy combined with latex condom with spermicide, latex condom with spermicide combined with a female partner who practices an acceptable method of contraception as indicated above); Men who are not sexually active (abstinent) but become active must use two of the listed contraceptive methods. Subjects who currently have or have had any acute illness within the past two weeks.
  • Subjects who currently have or have had within the past two weeks a poorly controlled chronic illness(anemia, thrombocytopenia, or coagulation disorders), cancer, infection, or any other clinically significant disorder.
  • Subjects who currently have or have had an autoimmune disease.
  • Subjects who have had within the past two weeks a symptomatic upper respiratory tract infection, nasopharyngitis, influenza or condition involving increase in nasal secretion such as seasonal or chronic, allergic rhinitis. Additionally, any subject with history of atopy/allergies within the past 30 days will be excluded.
  • Subjects with a history of serious psychiatric condition (depression, bipolar disorder, schizophrenia, suicidal ideation, or suicide attempts) or receiving two concomitant medications for the treatment of a psychiatric disorder or hospitalized for the treatment of a serious psychiatric disorder within six months of participation in the study.
  • Subjects with known skin photosensitivity.
  • Subjects with a personal or family history of porphyria.
  • Subjects with any open wound, lesion, inflammation, erythema, or infection affecting the nostrils, nose, upper lip, and area of skin close to the nose, including herpes simplex lesions and discoid lupus.
  • Subjects with a history of abnormal bleeding, bruising, frequent nosebleeds, or the diagnosis of von Willebrand disease.
  • Subjects with nasal polyps or significant anatomical nasal abnormality. Patients with deviated septa will be allowed in the study, provided the principal investigator does not deem a deviation to be of significant medical consequence. An ENT(Ear, Nose and Throat) specialist will be available for consult as needed.
  • Subjects with a history of nasal surgery, including cauterization, in the last 6 months.
  • Subjects with a history of multiple episodes [>3] of epistaxis within the 12 months prior to screening.
  • Subjects with in situ nasal jewelry or open nasal piercings.
  • Subjects with a known clinically significant history of atopy or hypersensitivity to any drug or latex or to ingredients of the nasal gel (such as benzalkonium chloride or other quaternary ammonium disinfectants) or to drugs related to XF-73.
  • Subjects known to have dermal sensitivity to chlorhexidine gluconate (CHG).
  • Subjects who have smoked within the month prior to screening.
  • Subjects who have been treated with or have taken any prescribed or over-the-counter medication daily for the last 14 days, with the exception of hormonal contraceptives or hormone replacement therapy.
  • Subjects who have taken or used topical or systemic antibiotics within the month prior to screening.
  • Subjects who have received an immunization within 30 days prior to screening.
  • Subjects with a history of drug or alcohol abuse in the last 12 months or who have a positive urine drug test for substances of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine metabolites, opiates, phencyclidine [PCP]) or alcohol.
  • Subjects who are known to have serum hepatitis, or who are carriers of the hepatitis B surface antigen(HBsAg) or hepatitis C (HCV) antibody, or who have a positive result to the test for human immunodeficiency virus (HIV) antibodies.
  • Subjects who have participated in a drug or vaccine clinical trial within the last month.
  • Subjects who have been exposed to XF-73 as part of a previous clinical trial.
  • Presence of any other condition or laboratory result that, in the opinion of the investigator would jeopardize the safety or rights of a subject participating in the trial or would render the subject unable to comply with the protocol.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01592214

Contacts
Contact: Mac Griffiss (330) 460-5030 jgriffiss@clinicalrm.com

Locations
United States, Ohio
Case Western Reserve University - Case Medical Center - Infectious Disease & HIV Medicine Recruiting
Cleveland, Ohio, United States, 44106-1716
Sponsors and Collaborators
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01592214     History of Changes
Other Study ID Numbers: 11-0007, N01AI80024C, XF-73
Study First Received: May 3, 2012
Last Updated: September 25, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Staphylococcus aureus, nasal decolonization, XF-73, gel formulation

Additional relevant MeSH terms:
Staphylococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Benzocaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 29, 2014