A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Safety, Tolerability and Pharmacokinetic Study of Topical Pirenzepine in Healthy Volunteers
WinSanTor Australia Pty Ltd
24 participants
May 10, 2017
Interventional
Conditions
Summary
This clinical trial aims to evaluate the safety and tolerability of 2 different pirenzepine formulations after daily topical dose administrations in healthy subjects for 14 days and of an alternative dosing regimen in healthy subjects with 1 of the pirenzepine topical formulations. The secondary purposes of this trial are to evaluate the pharmacokinetics (PK) of pirenzepine and its desmethyl metabolite following single and multiple topical doses of 2 different pirenzepine formulations and to evaluate the PK of pirenzepine and its desmethyl metabolite following an alternative dosing regimen with 1 of the pirenzepine topical formulations.
Eligibility
Inclusion Criteria11
- Male or female, 18-65 years old (inclusive).
- Body mass index (BMI) between 25 and 30 kg/m2 (inclusive).
- Be in general good health as determined by the Investigator, without clinically significant medical history.
- Normal or non-clinically significant findings on a physical examination, 12-lead electrocardiogram (ECG) and vital signs, as determined by the Investigator.
- Adequate hepatic and renal function, as determined by clinical laboratory assessments of blood and urine.
- Negative serum pregnancy test at Screening and negative urine pregnancy test on Day -1 for females of child bearing potential.
- Negative screen for drugs of abuse, cotinine, alcohol, hepatitis B surface antigen (HBs Ag), hepatitis C virus antibody (HCV Ab) and Human Immunodeficiency Virus (HIV) at Screening; and negative drugs of abuse, cotinine and alcohol screen on Day -1.
- Clinical laboratory values within the normal limits as defined by the clinical laboratory, unless the Investigator decides that out-of-range values are not clinically significant.
- Females of child-bearing potential and males must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 45 days following completion of therapy.
- Ability to provide written informed consent.
- Willing and able to follow study instructions and likely to complete all study requirements.
Exclusion Criteria17
- History of allergy or sensitivity to M1 antagonists or any of the components of the investigational product formulations.
- Known hypersensitivity to pirenzepine or another component of the investigational product.
- Have sensitive skin, as defined by a requirement to use soap and lotions formulated for ‘sensitive’ skin.
- Any open wound and/or sunburn(s) in the dosing area. Subjects who have a wound and/or sunburn at Screening which is anticipated to resolve before Day -1 can be enrolled.
- Any clinically significant central nervous system, cardiac, pulmonary, renal, gastrointestinal, respiratory, metabolic conditions (or history), or other pathological or physiological conditions, including a history of paralytic ileus, glaucoma, prostatic hypertrophy or tachycardia, that might interfere with the trial result in the Investigator’s opinion.
- Any condition, which in the Investigator’s opinion, puts the subject at significant risk, could confound the study results or may interfere significantly with the subject’s participation in the study.
- Use of any topical agents (prescription and over-the-counter, including lotions such as sunscreen, cosmetics, moisturizing lotion) at the administration site within a week before randomization and during confinement.
- History of serious skin diseases (as determined by the Investigator): such as skin cancer, psoriasis, eczema.
- History of urinary retention, as determined by previous diagnosis or patient self-reporting.
- Have received a tattoo in the dosing area within 12 months of dosing.
- Current smoker, or a history of regular (more than weekly) use of tobacco- or nicotine-containing products within 2 months prior to Screening.
- History of excessive alcohol intake (more than 4 standard drinks daily, on average) or use of recreational drugs within the last 3 months.
- Use of prescription or over-the-counter medications within 7 days of investigational product administration, with the exception of contraceptive medications, paracetamol, oral non-steroidal anti-inflammatory agents, and vitamins (if they do not exceed recommended daily dose), unless agreed as non-clinically relevant by the Investigator and Sponsor.
- Donation or loss of blood (excluding volume drawn at Screening) of 50 mL to 499 mL within 30 days of the study.
- Anticipated need for surgery or hospitalization during the study.
- Have completed another drug clinical trial within 45 days of dosing, or intend to participate in other drug clinical trials during this study period.
- Pregnant or nursing females.
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Interventions
This is a Phase 1, first in human, double-blind, randomized, placebo-controlled, multiple dose study consisting of a total of 24 healthy subjects: 3 cohorts of 8 subjects (6 subjects assigned to pirenzepine: 2 assigned to placebo in each cohort). Each treatment will be administered topically to the lower extremities (right and left calves [i.e., anterior lower leg/shins] and tops of feet) by study staff using gloved hands. The names of the 2 formulations that will be used are WinF90 (6.5% pirenzepine) and WinFB34 (4.0% pirenzepine). Cohort 1 will be administered 6.5% pirenzepine topical solution WinF90 or matching placebo – 5 mL applied once daily for 14 days. Cohort 2 will be administered 4.0% pirenzepine topical solution WinFB34 or matching placebo – 5 mL applied once daily for 14 days. Cohort 3 will be administered 4.0% pirenzepine topical solution WinFB34/matching placebo or 6.5% pirenzepine topical solution WinF90/matching placebo – administered for 14 days with dose volume and dose frequency to be determined following review of Cohort 1 and 2 data.
Locations(1)
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ACTRN12617000535370