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Also known as [14C]-GSK961081 oral solution
GSK961081 · 3 trials · 1 indication
The following PK parameter will be measured: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC\[0 inf\])
The following PK parameter will be measured: Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC\[0-t\]).
The following PK parameter will be measured: maximum observed plasma concentration (Cmax)
The following PK parameter will be measured: time of occurrence of Cmax (Tmax)
The following PK parameter will be measured: terminal phase half-life (t1/2)
| Arm | Type | Description |
|---|---|---|
| [14C]-GSK961081 IV+GSK961081 inhalation; [14C]-GSK961081 oral | EXPERIMENTAL | On Day 1 of Treatment Period 1, after an overnight fast of at least 8 hours, each subject will receive \[14C\] GSK961081 4 micrograms (mcg) by IV infusion over 1 hour. Within 5 minutes after the start of infusion, subjects will take 1200 mcg non-radiolabelled GSK961081 by inhalation. After Treatment Period 1, there will be a washout of at least 2 weeks. On Day 1 of Treatment Period 2, after an overnight fast of at least 8 hours, each subject will take 200 mcg \[14C\]-GSK961081 as an oral solution. |
| All subjects | EXPERIMENTAL | Eligible subjects will receive GSK961081 (400 micrograms or 1200 micrograms), GSK961081 matching placebo, propranolol (80 milligrams) and propranolol matching placebo in five treatment sessions through ten different crossover treatment sequences. There will be a washout period between treatment sessions of 7 to 14 days. |
| Sequence 1 | EXPERIMENTAL | 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. |
| Sequence 2 | EXPERIMENTAL | 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. |
| Sequence 3 | EXPERIMENTAL | 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. |
| Sequence 4 | EXPERIMENTAL | 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. |
| Sequence 5 | EXPERIMENTAL | 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. |
| Sequence 6 | EXPERIMENTAL | 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. |
| Sequence 7 | EXPERIMENTAL | 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. |
| Sequence 8 | EXPERIMENTAL | 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. |
| Name | Type | Description |
|---|---|---|
| [14C]-GSK961081 solution for IV infusion | DRUG | Subjects will receive 10 mL of solution equivalent to 4 mcg of \[14C\]-GSK961081 (approximately 6.2 kilobecquerel \[kBq\]) intravenously as a single dose over 1 hour. |
| [14C]-GSK961081 oral solution | DRUG | Subjects will receive 10 mL of solution equivalent to 200 mcg of \[14C\]-GSK961081 (approximately 311 kBq) orally as a single dose with up to 250 mL of water. |
| GSK961081 dry powder for inhalation | DRUG | Subjects will receive single dose of 4 actuations of 300 mcg GSK961081 per actuation (1200 mcg GSK961081 total) as inhalation immediately after the start of infusion. |
| GSK961081 | DRUG | GSK961081 multidose dry powder inhaler (Diskus inhaler) will be available with dosing strengths of 400 micrograms and 1200 micrograms administered once daily in the morning. |
| GSK961081 matching placebo | DRUG | GSK961081 matching placebo multidose dry powder inhaler (Diskus inhaler) will be available to be administered once daily in the morning. |
| Propranolol | DRUG | Propranolol over encapsulated tablet will be available with dosing strengths of 40 milligrams administered orally with 240 milliliters of water. |
| Propranolol matching placebo | DRUG | Propranolol matching placebo over encapsulated tablet will be available to be administered orally with 240 milliliters of water. |
Inclusion Criteria: * Between 30 and 55 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and ...
GSK961081 is an investigational small molecule being studied for Pulmonary Disease, Chronic Obstructive (COPD). It has been evaluated in Phase 1 clinical trials in healthy volunteers, not in patients with COPD. No approved indication exists for GSK961081.
GSK961081 is being developed by Theravance Biopharma, Inc., which trades on the Nasdaq under the ticker TBPH. The company has sponsored Phase 1 studies of the compound in the United Kingdom.
GSK961081 is in Phase 1 clinical development. All three of its registered trials are Phase 1 studies, and all three are completed. There are currently no active trials of GSK961081.
GSK961081 has been studied in three completed Phase 1 trials: NCT02663089, an ADME study in healthy subjects; NCT00687700, a pharmacology study of a dual pharmacophore in healthy volunteers; and NCT00550225, a study of a succinate salt version in healthy volunteers. All were conducted in the United Kingdom.
Yes, [14C]-GSK961081 oral solution is an alternative name for GSK961081. The carbon-14 labeled oral solution formulation was used in the absorption, distribution, metabolism, and excretion (ADME) study NCT02663089 to trace how the drug is processed in the body.