Succinate Salt Version of GSK961081 for Healthy Volunteers

A Randomised, Double-blind, Dose Escalating Study in Healthy Volunteers to Assess the Safety, Tolerability, Extra Pulmonary Pharmacodynamics and Pharmacokinetics of Single Doses of GSK961081 (Succinate Salt)

Salt Bridging study for GSK961081

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: GSK961081; Drug: GSK961081 matching placebo

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW10 7NS
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy adult males or female aged between 18 and 50 years.
• Body mass index within the range 19-29.9 kilograms/metre2
• Forced Expiratory Volume in 1 second (FEV1) >80% predicted and a FEV1/ Forced Vital Capacity (FVC) ratio > 0.7
• Subjects are current non-smokers who have not used any tobacco products in the 6-month period preceding the screening visit and have a pack history of < 10 pack years.

Exclusion criteria:

• Who have a past or present disease, which as judged by the Investigator and medical monitor may affect the outcome of the study or the safety of the subject
• History of respiratory disease
• Significant abnormal 12 lead ECG, QTc(B) and QTc(F) value at screening >450msec on an individual ECG or a PR interval outside the range 120-210 msec
• Supine mean heart rate outside the range 40-90 beats per minute (bpm) at screening.
• Subject has donated a unit of blood within the 56 days or intends to donate within 56 days after completing the study
• Subject is currently taking regular (or course of) medication whether prescribed or not (with the exception of contraceptives, including vitamins and herbal remedies such as St John's Wort.
• Subject has participated in a clinical study with a New Chemical Entity (NCE) within the past 3 months
• Infected with the Hepatitis B, Hepatitis C, or HIV virus
• Subject has a history of drug or other allergy, which, in the opinion of the Investigator, contraindicates their participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1; In session 1, subjects will receive 300 microgram GSK961081 succinate followed by placebo in session 2. The subjects will receive 1500 micrograms of GSK961081 succinate in session 3 and 1500 micrograms of GSK961081 edisylate in session 4.	Drug: GSK961081; GSK961081 edisylate and succinate will be administered as capsules via DISKUS inhaler formulated with lactose as a vehicle to make 12.5 milligrams. GSK961081 succinate will be given in a dose-ascending manner with a starting dose of 300 micrograms. The dose of GSK961081 edisylate is 1500 micrograms.; Drug: GSK961081 matching placebo; GSK961081 matching placebo formulated with lactose only as a vehicle to 12.5 milligrams will be administered via the DISKUS inhaler.
Experimental: Sequence 2; In session 1, subjects will receive 300 microgram GSK961081 succinate followed by 1500 micrograms of GSK961081 edisylate in session 2. The subjects will receive 1500 micrograms of GSK961081 succinate in session 3 and placebo in session 4.	Drug: GSK961081; GSK961081 edisylate and succinate will be administered as capsules via DISKUS inhaler formulated with lactose as a vehicle to make 12.5 milligrams. GSK961081 succinate will be given in a dose-ascending manner with a starting dose of 300 micrograms. The dose of GSK961081 edisylate is 1500 micrograms.; Drug: GSK961081 matching placebo; GSK961081 matching placebo formulated with lactose only as a vehicle to 12.5 milligrams will be administered via the DISKUS inhaler.
Experimental: Sequence 3; In session 1, subjects will receive 300 microgram GSK961081 succinate followed by placebo in session 2. The subjects will receive 1500 micrograms of GSK961081edisylate in session 3 and an additional dose of GSK961081 succinate in session 4.	Drug: GSK961081; GSK961081 edisylate and succinate will be administered as capsules via DISKUS inhaler formulated with lactose as a vehicle to make 12.5 milligrams. GSK961081 succinate will be given in a dose-ascending manner with a starting dose of 300 micrograms. The dose of GSK961081 edisylate is 1500 micrograms.; Drug: GSK961081 matching placebo; GSK961081 matching placebo formulated with lactose only as a vehicle to 12.5 milligrams will be administered via the DISKUS inhaler.
Experimental: Sequence 4; In session 1, subjects will receive 300 microgram GSK961081 succinate followed by 1500 micrograms of GSK961081 edisylate in session 2. The subjects will receive placebo in session 3 and an additional dose of GSK961081 succinate in session 4.	Drug: GSK961081; GSK961081 edisylate and succinate will be administered as capsules via DISKUS inhaler formulated with lactose as a vehicle to make 12.5 milligrams. GSK961081 succinate will be given in a dose-ascending manner with a starting dose of 300 micrograms. The dose of GSK961081 edisylate is 1500 micrograms.; Drug: GSK961081 matching placebo; GSK961081 matching placebo formulated with lactose only as a vehicle to 12.5 milligrams will be administered via the DISKUS inhaler.
Experimental: Sequence 5; In session 1, subjects will receive 1500 micrograms of GSK961081 edisylate followed by 900 microgram GSK961081 succinate in session 2. The subjects will receive 1500 micrograms of GSK961081 succinate in session 3 and placebo in session 4.	Drug: GSK961081; GSK961081 edisylate and succinate will be administered as capsules via DISKUS inhaler formulated with lactose as a vehicle to make 12.5 milligrams. GSK961081 succinate will be given in a dose-ascending manner with a starting dose of 300 micrograms. The dose of GSK961081 edisylate is 1500 micrograms.; Drug: GSK961081 matching placebo; GSK961081 matching placebo formulated with lactose only as a vehicle to 12.5 milligrams will be administered via the DISKUS inhaler.
Experimental: Sequence 6; In session 1, subjects will receive placebo followed by 900 micrograms of GSK961081 succinate in session 2. The subjects will receive 1500 micrograms of GSK961081 succinate in session 3 and 1500 micrograms of GSK961081 edisylate in session 4.	Drug: GSK961081; GSK961081 edisylate and succinate will be administered as capsules via DISKUS inhaler formulated with lactose as a vehicle to make 12.5 milligrams. GSK961081 succinate will be given in a dose-ascending manner with a starting dose of 300 micrograms. The dose of GSK961081 edisylate is 1500 micrograms.; Drug: GSK961081 matching placebo; GSK961081 matching placebo formulated with lactose only as a vehicle to 12.5 milligrams will be administered via the DISKUS inhaler.
Experimental: Sequence 7; In session 1, subjects will receive 1500 micrograms of GSK961081 edisylate followed by 900 microgram GSK961081 succinate in session 2. The subjects will receive placebo in session 3 and an additional dose of GSK961081 succinate in session 4.	Drug: GSK961081; GSK961081 edisylate and succinate will be administered as capsules via DISKUS inhaler formulated with lactose as a vehicle to make 12.5 milligrams. GSK961081 succinate will be given in a dose-ascending manner with a starting dose of 300 micrograms. The dose of GSK961081 edisylate is 1500 micrograms.; Drug: GSK961081 matching placebo; GSK961081 matching placebo formulated with lactose only as a vehicle to 12.5 milligrams will be administered via the DISKUS inhaler.
Experimental: Sequence 8; In session 1, subjects will receive placebo followed by 900 microgram GSK961081 succinate in session 2. The subjects will receive 1500 micrograms of GSK961081 edisylate in session 3 and an additional dose of GSK961081 succinate in session 4.	Drug: GSK961081; GSK961081 edisylate and succinate will be administered as capsules via DISKUS inhaler formulated with lactose as a vehicle to make 12.5 milligrams. GSK961081 succinate will be given in a dose-ascending manner with a starting dose of 300 micrograms. The dose of GSK961081 edisylate is 1500 micrograms.; Drug: GSK961081 matching placebo; GSK961081 matching placebo formulated with lactose only as a vehicle to 12.5 milligrams will be administered via the DISKUS inhaler.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
FEV1 at intervals	during the 10 week study
Cardiac monitoring at intervals	during the 10 week study

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma concentrations of GSK961081 at intervals	during the 10 week study
PK parameters at intervals	during the 10week study

Collaborators and Investigators

• Sponsor: Theravance Biopharma
• Collaborators: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2007
• Primary Completion (Actual): January 8, 2008
• Study Completion (Actual): January 8, 2008

Study Registration Dates

• First Submitted: October 26, 2007
• First Submitted That Met QC Criteria: October 26, 2007
• First Posted (Estimate): October 29, 2007

Study Record Updates

• Last Update Posted (Actual): October 6, 2021
• Last Update Submitted That Met QC Criteria: September 28, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: succinate; anti-muscarinic; b-agonist
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: MAB108115

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: MAB108115
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: MAB108115
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: MAB108115
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: MAB108115
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: MAB108115
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: MAB108115
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Informed Consent Form
   Information identifier: MAB108115
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register