OLP-1002 is Being Studied in the Treatment of Pain.

Pain Clinical Trial

Official title:

OLP-1002 - A First-in-human, Double-blind, Placebo-controlled, Single and Multiple Subcutaneous Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Male and Female Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03760913
• Other study ID #: OLP-1002-001
• Status: Completed
• Phase: Early Phase 1
• Start date: November 21, 2018
• Est. completion date: October 16, 2020

Study information

• Verified date: November 2020
• Source: OliPass Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to assess the safety and tolerability of single and multiple subcutaneous doses of OLP-1002 in healthy subjects.

Description:

The exploratory objectives of the study are to evaluate the pharmacodynamic effect of OLP-1002 following single subcutaneous doses in healthy volunteers using a capsaicin pain model, and to monitor the effects of a single subcutaneous doses of OLP-1002 on cardiac QT interval. Where possible, single and/or multiple subcutaneous dose pharmacokinetics of OLP-1002 in healthy subjects will be determined.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: October 16, 2020
• Est. primary completion date: October 16, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Healthy male or females of any race, between 18 and 60 years of age, inclusive.

• Body mass index between 18.0 and 28.0 kg/m², inclusive.

• In good health, determined by no clinically significant findings from medical history, physical examination, single 12-lead electrocardiogram (resting heart rate > 45 bpm and < 90 bpm), vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [eg, suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) at Screening as assessed by the Investigator (or designee).

• Willing to abide by the contraception requirements.

• Able to comprehend and willing to sign an Informed Consent Form and to abide by the study restrictions.

Exclusion Criteria:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).

• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).

• Any of the following:

• QT interval corrected for heart rate using Fridericia's method > 450 ms confirmed by repeat measurement.

• QRS duration > 110 ms confirmed by repeat measurement.

• PR interval > 220 ms confirmed by repeat measurement.

• findings which would make QT interval corrected for heart rate measurements difficult or QT interval corrected for heart rate data uninterpretable.

• history of additional risk factors for torsades de pointes (eg, heart failure, hypokalemia, family history of long QT syndrome).

• Female subjects who are pregnant or breastfeeding.

• History of alcoholism or drug/chemical abuse within 1 year prior to Screening.

• Alcohol consumption of > 21 units per week for males and >14 units per week for females. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.

• Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at Screening or Check-in.

• Positive hepatitis panel and/or positive human immunodeficiency virus test.

• Active skin conditions such as dermatitis, allergy, eczema, psoriasis, or abnormal healing.

• Tattoos, scars, or moles that in the opinion of the Investigator are likely to interfere with dosing or study assessments at any of the potential injection sites.

• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days or 5 half-lives of the investigational product, whichever is longer, prior to Check-in.

• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to Check-in, unless deemed acceptable by the Investigator (or designee).

• Use or intend to use any prescription medications/products other than hormone replacement therapy, oral, implantable, transdermal, injectable, or intrauterine contraceptive concomitant medications within 14 days prior to Check-in, unless deemed acceptable by the Investigator (or designee).

• Use or intend to use slow-release medications/products considered to still be active within 14 days prior to Check-in, unless deemed acceptable by the Investigator (or designee).

• Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 7 days prior to Check-in, unless deemed acceptable by the Investigator (or designee) and/or Sponsor have given their prior consent.

• Use of tobacco- or nicotine-containing products within 3 months prior to Check-in.

• Receipt of blood products within 60 days prior to Check-in.

• Donation of blood from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.

• Poor peripheral venous access.

• Have previously completed or withdrawn from this study or any other study investigating OLP-1002, and have previously received the investigational product.

• Subjects who, in the opinion of the Investigator (or designee), should not participate in this study.

• Part A - PD assessment groups only

• Subjects considered non-acceptable responders to the intradermal capsaicin test at screening, defined as maximum VAS score of < 3.0 or > 9.0.

Related Conditions & MeSH terms

• Pain

Intervention

Drug:
• OLP-1002 (Test): Part A, Single Ascending Dose
Subcutaneous Injection: 30 ng, 120 ng, 400 ng, 1.2 µg, 3 µg, 6 µg, 12 µg, 20 µg, 40 µg, 80 µg, 160 µg
• OLP-1002 (Test): Part B, Multiple Ascending Dose
Subcutaneous Injection: 5 x 2 µg, 5 x 5 µg, 5 x 10 µg, 5 x 20 µg, 5 x 40 µg, 5 x 80 µg

Other:
• Placebo: Placebo Part A, Single Ascending Dose
Subcutaneous Injection: Placebo
• Placebo: Placebo Part B, Multiple Ascending Dose
Subcutaneous Injection: Placebo x 5

Locations

Country	Name	City	State
United Kingdom	Leeds CRU	Leeds

Sponsors (1)

Lead Sponsor	Collaborator
OliPass Corporation

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events Stratified by Overall and Severity	Participants were observed for any signs or symptoms of adverse events and asked about their condition by open questioning, such as "How have you been feeling since you were last asked?", at least once each day while resident at the study site and at each study visit.	Part A: From screening through study completion, up to 32 days. Part B: From screening through study completion, up to 60 days.
Primary	Number of Participants Who Experienced Clinically Important Changes in Supine Diastolic and Systolic Blood Pressure	Number of participants who experienced clinically important changes from baseline (the last value recorded prior to first dose) to scheduled timepoints in supine diastolic and systolic blood pressure.; Participants were supine for at least 5 minutes before blood pressure measurements. Blood pressure was measured in triplicate and the time of measurement are below: Single ascending dose: Predose, 1, 2, 4, 8, 24 (± 1 hours), and 48 hours posdose Multiple ascending dose: Day 1 (Predose, 1, 2, 4, and 8 hours postdose), Day 2, Day 4 (postdose), Day 5, Day 7 (postdose), Day 9, Day 10 (postdose), Day 12, Day 13 (predose, 1, 2, 4, and 8 hours postdose), and Day 15; No treatment or dose related trends and no clinically significant changes were observed in mean or individual participant supine blood pressure.; Supine diastolic blood pressure reference range: 90 to 140 mmHg. Supine systolic blood pressure reference range: 50 to 90 mmHg.	Part A: From screening through study completion, up to 32 days. Part B: From screening through study completion, up to 60 days.
Primary	Number of Participants Who Experienced Clinically Important Changes in Supine Pulse Rate	Number of participants who experienced clinically important changes from baseline (the last value recorded prior to first dose) to scheduled timepoints in supine pulse rate.; Participants were supine for at least 5 minutes before pulse rate measurements. Pulse rate was measured in triplicate and the time of measurement are below: Single ascending dose: Predose, 1, 2, 4, 8, 24 (± 1 hours), and 48 hours posdose Multiple ascending dose: Day 1 (Predose, 1, 2, 4, and 8 hours postdose), Day 2, Day 4 (postdose), Day 5, Day 7 (postdose), Day 9, Day 10 (postdose), Day 12, Day 13 (predose, 1, 2, 4, and 8 hours postdose), and Day 15; No treatment or dose related trends and no clinically significant changes were observed in mean or individual participant supine pulse rate.; Reference range: 40 to 100 beats per minute.	Part A: From screening through study completion, up to 32 days. Part B: From screening through study completion, up to 60 days.
Primary	Number of Participants Who Experienced Clinically Important Changes in Respiratory Rate	Number of participants who experienced clinically important changes from baseline (the last value recorded prior to first dose) to scheduled timepoints in respiratory rate.; Participants were supine for at least 5 minutes before respiratory rate measurements. Respiratory rate was measured in triplicate and the time of measurement are below: Single ascending dose: Predose, 1, 2, 4, 8, 24 (± 1 hours), and 48 hours posdose Multiple ascending dose: Day 1 (Predose, 1, 2, 4, and 8 hours postdose), Day 2, Day 4 (postdose), Day 5, Day 7 (postdose), Day 9, Day 10 (postdose), Day 12, Day 13 (predose, 1, 2, 4, and 8 hours postdose), and Day 15; No treatment or dose related trends and no clinically significant changes were observed in mean or individual participant respiratory rate.; Reference range: 10 to 24 breaths per minute.	Part A: From screening through study completion, up to 32 days. Part B: From screening through study completion, up to 60 days.
Primary	12-lead Electrocardiogram Parameters	Resting 12-lead electrocardiogram parameters were recorded after the participant had been supine and at rest for at least 5 minutes.; Baseline: the last value recorded prior to first dose; QTcB: QT interval corrected for heart rate using Bazett's formula; QTcF: QT interval corrected for heart rate using Fridericia's method.	Part A: From screening through study completion, up to 32 days. Part B: From screening through study completion, up to 60 days.
Primary	Number of Participants With Findings of Clinical Importance in Clinical Chemistry, Hematology, and Urinalysis Test Results	Number of participants with findings of clinical importance in clinical chemistry, hematology, and urinalysis test results.; Clinical laboratory evaluations included: Clinical chemistry: Alanine aminotransferase; Albumin; Alkaline phosphatase; Aspartate aminotransferase; Calcium; Chloride; Cholesterol; Creatinine; Direct bilirubin; Gamma-glutamyl transferase; Glucose; Inorganic phosphate; Potassium; Sodium; Total bilirubin; Total protein; Urea Hematology: Hematocrit; Hemoglobin; Mean cell hemoglobin; Mean cell hemoglobin concentration; Mean cell volume; Platelet count; Red blood cell count; White blood cell count; White blood cell differential (Basophils; Eosinophils; Lymphocytes; Monocytes; Neutrophils) Urinalysis: Blood; Glucose; Ketones; pH; Protein; Specific gravity; Urobilinogen; Microscopic examination	Part A: From screening through study completion, up to 32 days. Part B: From screening through study completion, up to 60 days.
Primary	Number of Participants With Full and Symptom-Directed Physical Examination Results	A full physical examination and symptom-directed physical examinations were performed at specified timepoints.	Part A: From screening through study completion, up to 32 days. Part B: From screening through study completion, up to 60 days.
Primary	Number of Participants With Injection Site Assessment Results	Evaluation of the dosing site for the following: Pain: Grade 0 to 4 Redness (assessed by estimating the size of the red patch at the injection site across its widest point): Grade 0: 0-24 mm; Grade 1: 25-50 mm; Grade 2: 51-100 mm; Grade 3: More than 100 mm; Grade 4: Requires medical intervention greater than analgesia Swelling (assessed by estimating the size of the raised area around the injection site across its widest point): Grade 0: 0-24 mm; Grade 1: 25-50 mm and does not interfere with activity; Grade 2: 51-100 mm or interferes with activity; Grade 3: More than 100 mm and prevents daily activity; Grade 4: Requires medical intervention greater than analgesia Tenderness: Grade 0 to 4; Bruising and ulceration were evaluated as present or absent.	Part A: From screening through study completion, up to 32 days. Part B: From screening through study completion, up to 60 days.
Primary	Number of Participants With Exposure to OLP-1002 That Exceeded Pre-define Exposure Limits From Non-clinical Studies	Participants were assessed to demonstrate that exposure to OLP-1002 did not exceed pre-defined exposure limits from non-clinical studies. Participants with temporary detected plasma concentrations between the low limit of detection [0.2 ng/mL] and lower limit of quantification [1 ng/mL] are presented in the results.	Part A: Day 1 postdose. Part B: Day 1 postdose and Day 13 postdose.