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| ID | Type | Description | Link |
|---|---|---|---|
| QSC205141 | Other Identifier | Quotient Sciences |
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| Name | Class |
|---|---|
| Quotient Sciences | INDUSTRY |
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The aim of this early phase two-part study was to compare the bioavailability (BA) pharmacokinetics (PK) and pharmacodynamics (PD) of racemic pindolol with the benzoate salt of the S-enantiomer of pindolol (ACM-001.1) and provide safety information. A total of 51 healthy male and female subjects were enrolled, and 48 healthy subjects completed the study.
Part 1 consisted of two Groups to compare BA and PK, Group 1 received two treatment sequences of a single dose of ACM-001.1 versus racemic pindolol; Group 2 ran in parallel with Group 1 and assessed the PK of a single dose of racemic pindolol in a single period.
Part 2 consisted of four groups, to evaluate the steady state PK and PD of ACM-001.1 with multiple ascending doses over 4 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 Group1 (AB) | Experimental | Part 1 Group1 Subjects were randomised to two treatment regimens (A and B) and received treatment sequence AB in a 2-period cross over. Regimen A = 15 mg ACM-001.1 and matching placebo. Regimen B = 30 mg pindolol. |
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| Part 1 Group 1 (BA) | Experimental | Subjects were randomised to two treatment regimens (A and B) and received treatment sequence BA in a 2-period cross over. Regimen B = 30 mg pindolol. Regimen A = 15 mg ACM-001.1 and matching placebo. |
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| Part 1 Group 2 (C) | Experimental | Subjects were non-randomised; received regimen C in parallel with Group 1 in a single period. Regimen C = 15 mg pindolol. |
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| Part 2 Group D | Experimental | Subjects received one of the four regimens over a four day treatment period. Regimen D = 20 mg pindolol BID (bis in die) for four days. |
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| Part 2 Group E |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Part 1 Group 1 Regime A (ACM-001.1) | Drug | Drug: ACM-001.1 immediate release tablets for oral use and matching placebo, and pindolol tablets for oral use. Subjects randomised to Regimen A received placebo tablets to match the tablet number received by subjects in Regimen B. |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1 Composite of PK parameters following single doses | Comparative bioavailability of S- pindolol and pindolol include: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinite]. | Up to 5 days |
| Part 1 PK parameters following single doses | Comparative bioavailability of S- pindolol and pindolol include:maximum observed concentration (Cmax) | Up to 5 days |
| Part 1 PK parameters following single doses | Comparative bioavailability of S- pindolol and pindolol include:time of occurrence of Cmax (Tmax) | Up to 5 days |
| PK parameters following single doses | Comparative PK parameters of S- pindolol and racemic pindolol include: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinite]). | Up to 5 days |
| PK parameters following single doses | Comparative PK parameters of S- pindolol and racemic pindolol include: maximum observed concentration (Cmax) | Up to 5 days |
| PK parameters following single doses | Comparative PK parameters of S- pindolol and racemic pindolol include: t time of occurrence of Cmax (Tmax) | Up to 5 days |
| Stoichiometric dose relationship measured using PK parameters following single doses |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1 Composite PK parameters in urine following single doses | PK parameters of S-pindolol, R-pindolol and pindolol: Amount excreted (Ae), Cumulative amount excreted (CumAe), Fraction of dose excreted (%Ae) and Cumulative fraction of dose excreted (%CumAe) | Up to 5 days |
| Part 2 Composite PK parameters in urine following multiple doses and pindolol |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Quotient Sciences Ltd | Ruddington | NG11 9JS | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39665235 | Derived | Misselwitz F, Henderson D, Menakuru SR, Morten E, Roe C, Whitaker G, Wohlfeil S, McDermott J. Pharmacokinetics, Pharmacodynamics and Bioavailability of ACM-001.1 (S-Pindolol Benzoate) in Healthy Volunteers. J Cachexia Sarcopenia Muscle. 2025 Feb;16(1):e13651. doi: 10.1002/jcsm.13651. Epub 2024 Dec 12. |
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Part 1: part - blinded, part randomized, partial cross- over study. Group 1: double - blinded and randomized to two treatment sequences in a two period cross- over.
Group 2: open label, non-randomized and in parallel with Group 1. Part 2: single-blind (subject blinded), randomized, parallel-group.
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Part 2 was single - blind study (subject blinded). Masking was not triple for all parts of the study or all arms.
Subjects received one of the four regimens over a four day treatment period. Regimen E = 5 mg ACM-001.1 and placebo BID for four days. |
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| Part 2 Group F | Experimental | Subjects received one of the four regimens over a four day treatment period. Regimen F = 10 mg ACM-001.1 and placebo BID for four days. |
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| Part 2 Group G | Experimental | Subjects received one of the four regimens over a four day treatment period. Regimen G = 15 mg ACM-001.1 and placebo BID for four days. |
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| Part 1 Group 2 Regimen C (Pindolol) | Drug | Drug: Pindolol tablets for oral use. |
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| Part 2 Group D (Pindolol) | Drug | Drug: Pindolol tablets for oral use. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D. |
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| Part 2 Group E (ACM-001.1) | Drug | Drug: ACM-001.1 immediate release tablets for oral use and matching placebo. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D. |
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| Part 2 Group F (ACM-001.1 ) | Drug | Drug: ACM-001.1 immediate release tablets for oral use and matching placebo. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D. |
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| Part 2 Group G (ACM-001.1) | Drug | Drug: ACM-001.1 immediate release tablets for oral use and matching placebo. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D. |
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| Part 1 Group 1 Regimen B (Pindolol) | Drug | Drug: pindolol tablets for oral use. Subjects randomised to Regimen A received placebo tablets to match the tablet number received by subjects in Regimen B. |
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| Part 1 Group 1 Regimen A (Placebo) | Other | Placebo for oral use. Subjects randomised to Regimen A received placebo tablets to match the tablet number received by subjects in Regimen B. |
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| Part 2 Group E (Placebo) | Other | Placebo for oral use. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D. |
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| Part 2 Group F (Placebo) | Other | Placebo for oral use. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D. |
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| Part 2 Group G ( Placebo) | Other | Placebo for oral use. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D. |
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PK parameters of S- pindolol and racemic pindolol include: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinite])
| Up to 5 days |
| Stoichiometric dose relationship measured using PK parameters following single doses | PK parameters of S- pindolol and racemic pindolol include: maximum observed concentration (Cmax). | Up to 5 days |
| Part 2 Composite of PK parameters following multiple doses in plasma | PK parameters of S- pindolol/racemic pindolol:Area under the curve for interval between doses (tau) (AUC(0 tau);Area under the concentration-time curve from time zero (pre-dose) to last time of measurable concentration (AUC[0-t]) | Up to 6 days |
| Part 2 Composite of PK parameters following multiple doses in plasma | PK parameters of S- pindolol/racemic pindolol: Maximum observed concentration (Cmax), | Up to 6 days |
| Part 2 Composite of PK parameters following multiple doses in plasma | PK parameters of S- pindolol/racemic pindolol: Time to first occurrence of Cmax from plasma concentration-time data(Tmax). | Up to 6 days |
| Pharmacodynamics of ACM-001.1: Cardiovascular vital parameter- heart rate | Heart rate (beats per minute) | Up to 6 days |
| Cardiovascular vital parameter- blood pressure | Systolic blood pressure (mmHG) and diastolic blood pressure (mmHG) | Up to 6 days |
| Serum biomarker- DHEA/Cortisol | Dehydroepiandrosterone (DHEA)/Cortisol (ng/mL). Serum concentrations were determined using validated analytical method. | Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours |
| Serum biomarker- Myostatin | Myostatin (pg/mL).Serum concentrations were determined using validated analytical method. | Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours. |
| Serum biomarker- Folistatin | Folistatin (pg/mL).Serum concentrations were determined using validated analytical method. | Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours. |
| Serum biomarker-IGF1 | Insulin-like growth factor (IGF)1 (pg/mL).Serum concentrations were determined using validated analytical method. | Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours. |
| Serum biomarker - (Type 3 procollagen peptide) PIIINP | PIIINP (pg/mL).Serum concentrations were determined using validated analytical method. | Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours. |
| Serum biomarker - monokine-induced by gamma interferon (MIG/CXL9) Leptin | Leptin (pg/mL).Serum concentrations were determined using validated analytical method. | Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours. |
| Serum biomarker - epithelial neutrophil activating peptide 78 (ENA78) | ENA78 (pg/mL).Serum concentrations were determined using validated analytical method. | Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours. |
| Serum biomarker - Ghrelin | Ghrelin (pg/mL).Serum concentrations were determined using validated analytical method. | Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours. |
| Serum biomarker - Growth Hormone Receptor Hormone | Growth Hormone Receptor Hormone (ng/mL).Serum concentrations were determined using validated analytical method. | Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours. |
| Serum biomarker - Somatostatin | Somatostatin (pg/mL).Serum concentrations were determined using validated analytical method. | Day 1 at pre-dose (baseline). Day 4 at pre-dose, 1.5 hours. |
PK parameters of S-pindolol, R-pindolol and pindolol: Amount excreted (Ae), Cumulative amount excreted (CumAe), Fraction of dose excreted (%Ae) and Cumulative fraction of dose excreted (%CumAe) |
| Up to 7 days |
| Part 1 and Part 2 Analysis of S-pindolol and R-pindolol concentrations in plasma for any in vivo conversion | Plasma concentrations were determined using validated analytical methods. | Up to 4 days |
| Part 1 Number of participants with adverse events following single doses as a measure of safety and tolerability | AEs will be collected from provision of written informed consent until discharge at the follow-up contact. | From screening: day -28 to follow up call on day 8 (part 1), up to 36 days. |
| Part 2 Number of participants with adverse events following single doses as a measure of safety and tolerability | AEs will be collected from provision of written informed consent until discharge at the follow-up contact | From screening: day -28 to follow up call on day 11 (part 2), up to 39 days. |
| Part 2 only - Pulmonary function test | Forced expiratory spirometry to determine parameters FEV1, FVC, FEV1/FVC | Up to 32 days |
| ID | Term |
|---|---|
| D002100 | Cachexia |
| ID | Term |
|---|---|
| D015431 | Weight Loss |
| D001836 | Body Weight Changes |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D013851 | Thinness |
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| ID | Term |
|---|---|
| D010869 | Pindolol |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
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