A Study to Test the Safety/Tolerability of Increasing Doses of LNP1892 Versus Placebo in Healthy Male/Female Subjects

LNP1892 - A Phase I, Double-Blind, Placebo-Controlled, Ascending Single and Multiple Oral Dose, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study in Healthy Male and Female Subjects

The purpose of this study is to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending oral dose LNP1892 in healthy males and female subjects

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: LNP1892

Detailed Description

This is first in human, Phase 1 study. Primary purpose is to assess safety, tolerability, pharmacodynamic and pharmacokinetic of the LNP1892. Study will be conducted in healthy human subjects. Pharmacokinetic will be studied in the subjects after administration of single and multiple doses.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS2 9LH
    • Covance Clinical Research Unit Ltd. Springfield House Hyde Street

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects will be; males or females (Group A3 only), of any ethnic origin, between 18 and 65 years of age (both inclusive)
• Subjects will have a body mass index (BMI) between 18.0 and 32.0 kg/m2 inclusive
• Subjects must be in good health, as determined by; medical history, physical examination, vital sign assessment, 12-lead electrocardiogram (ECG)
• Clinical laboratory evaluations (congenital non-haemolytic hyperbilirubinaemia is not acceptable)
• Subjects will have given their written informed consent to participate in the study and to abide by the study restrictions

Exclusion Criteria:

• Male subjects who are not willing, or whose partners are not willing, to use appropriate contraception until 3 months after the final dosing occasion.
• Female subjects who are of child-bearing potential; or those with tubal ligation.
• Subjects who have donated; blood in the 3 months prior to screening, plasma in the 7 days prior to screening, platelets in the 6 weeks prior to screening
• Subjects who;consume alcohol, cigarettes, tobacco and have a significant history of alcoholism or drug/chemical abuse as determined by the Investigator
• Subjects who have used any non-prescribed systemic or topical medication, herbal remedies, Vitamin supplements, mineral supplements within 7 days of the first dose administration.
• Subjects who have received any medications, within 30 days of the first dose administration, or any prescribed systemic or topical medication within 14 days of the first dose administration
• Subjects who have an abnormality in heart rate, blood pressure, temperature or respiration rate.
• Subjects with; a positive urine drug screen, a positive alcohol breath test result at screening or first admission.
• Subjects who have an abnormality in the 12-lead ECG.
• Female subjects who are pregnant or lactating
• Subjects who are participating in a clinical study or who have participated in a clinical study involving administration of an investigational drug (new molecular entity) in the past 3 months.
• Subjects with a significant history of drug allergy to similar drug or its excipients.
• Subjects who have any clinically significant medical history or significant allergic condition in the opinion of the investigator
• Subjects with clinically significant out of range PTH or serum calcium or vitamin D levels as judged by the investigator. Subjects with current or a history of hypocalcaemia
• Subjects who; are known to have serum hepatitis, are carriers of the hepatitis B surface antigen (HBsAg) are carriers of the hepatitis C antibody, have a positive result to the test for HIV antibodies.
• Subjects who have previously taken part in or withdrawn from this study post first drug administration.
• Other standard exclusion criteria like Subjects who have a clinically significant disorder or a significant abnormal laboratory finding, in the opinion of the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LNP1892; Dosage Form: Tablet Two Parts. Part A: Single Ascending Dose (SAD) starting with 25 mg (Maximum 5 cohorts). Part B: Multiple Ascending Dose (MAD), 10 days dosing, Maximum 3 cohorts. Six subjects in each cohort will receive LNP1892	Drug: LNP1892; Tablets of two strengths (5 and 25 mg)
Placebo Comparator: Placebo; Two subjects in each cohort will receive matching placebo.	Drug: Placebo; Matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the safety and tolerability of single and multiple oral doses of LNP1892 in healthy subjects	Up to 30 days after last dose

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the single and multiple oral dose pharmacokinetics of LNP1892 in healthy subjects	Pre-dose to 72 hours post last dose
To determine the single and multiple oral dose pharmacodynamics of LNP1892 in healthy subjects.	Pre-dose to 72 hours post last dose

Other Outcome Measures

Outcome Measure	Time Frame
Exploratory Objectives: To determine the effect of food on the single oral dose pharmacokinetics of LNP1892 in healthy subjects	Pre-dose to 72 hours post last dose
Exploratory Objectives: To determine the effect of gender on the single oral dose pharmacokinetics of LNP1892 in healthy subjects	Pre-dose to 72 hours post last dose

Collaborators and Investigators

• Sponsor: Lupin Ltd.
• Investigators: Study Director: Jim Bush, MB ChB, PhD, Covance

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: June 24, 2014
• First Submitted That Met QC Criteria: June 24, 2014
• First Posted (Estimate): June 25, 2014

Study Record Updates

• Last Update Posted (Estimate): April 13, 2015
• Last Update Submitted That Met QC Criteria: April 10, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Phase 1, safety, tolerability, PK, PD
• Other Study ID Numbers: LRP/LNP1892/2014/001; 2014-000327-24 (EudraCT Number)