Clotting factor preparations for delivery into tissue of the intestinal tract using a swallowable drug delivery device
Embodiments provide devices, preparations and methods for delivering therapeutic agents (TAs) such as clotting factors (CFs, e.g., Factor 8) within the GI tract. Many embodiments provide a swallowable device e.g., a capsule for delivering TAs into the intestinal wall (IW). Embodiments also provide TA preparations configured to be contained within the capsule, advanced from the capsule into the IW and/or surrounding tissue (ST) and degrade to release the TA into the bloodstream to produce a therapeutic effect (e.g., improved clotting). The preparation can be operably coupled to delivery means having a first configuration where the preparation is contained in the capsule and a second configuration where the preparation is advanced out of the capsule into the IW or ST (e.g., the peritoneal cavity). Embodiments are particularly useful for delivery of CFs for treatment of clotting disorders (e.g., hemophilia) where such CFs are poorly absorbed and/or degraded within the GI tract.
1. A swallowable device for treating a clotting factor disorder in a patient, the swallowable device comprising:
a swallowable capsule;
a clotting factor preparation disposed in the capsule, the preparation comprising a tissue penetrating member and a clotting factor in a solid and biologically active form that promotes or accelerates clotting in the patient, the clotting factor being disposed in, or formed into the shape of, the tissue penetrating member; and
an actuation mechanism operably coupled to the preparation;
wherein the actuation mechanism has a first configuration and a second configuration, the preparation being contained within the capsule in the first configuration and advanced out of the capsule by an application of force from the actuation mechanism on the tissue penetrating member such that the preparation is advanced through the intestinal wall of the patient and inserted into a peritoneal cavity of the patient after oral ingestion of the capsule;
wherein after insertion, the tissue penetrating member is retained in the peritoneal cavity where the tissue penetrating member is degraded in serosal fluids of the peritoneal cavity to release the clotting factor in its biologically active form into the blood stream to treat the clotting disorder by promoting or accelerating clotting in the patient.
2. The device of claim 1 , wherein the tissue penetrating member has sufficient column strength to be advanced through the intestinal wall and into the peritoneal cavity by the application of force.
3. The device of claim 1 , wherein the tissue penetrating member is structured as a shaft having a pointed end.
4. The device of claim 3 , wherein the pointed end is straight.
5. The device of claim 3 , wherein the tissue penetrating member includes a degradation feature configured to enhance a rate of degradation of the tissue penetrating member in the serosal fluids of the peritoneal cavity.
6. The device of claim 5 , wherein the degradation feature comprises an aperture in the tissue penetrating member.
7. The device of claim 5 , wherein the degradation feature comprises a channel in a surface of the tissue penetrating member.
8. The device of claim 5 , wherein the degradation feature is positioned such that the tissue penetrating member maintains sufficient column strength to be advanced through the intestinal wall and into the peritoneal cavity by the application of force on an end of the tissue penetrating member.
9. The device of claim 5 , wherein the degradation feature is positioned and configured to facilitate fracture or breakage of the tissue penetrating member by forces applied by the patient's body to the peritoneal cavity.
10. The device of claim 1 , wherein the force of the application of force on the tissue penetrating member is a mechanical force.
11. The device of claim 1 , wherein the actuation mechanism comprises an expandable member.
12. The device of claim 11 , wherein the expandable member comprises a spring.
13. The device of claim 11 , wherein the expandable member comprises an expandable balloon.
14. The device of claim 1 , wherein the capsule comprises a biodegradable material configured to degrade by contact with fluids in the gastro-intestinal (GI) tract of the patient.
15. The device of claim 14 , wherein the capsule further comprises an outer coating or layer configured to degrade at a selected pH in the GI tract of the patient.
16. The device of claim 15 , wherein the selected pH corresponds to a location in the small intestine of the patient.
17. The device of claim 1 , wherein the clotting factor comprises Factor VIII (F8) or a Factor VIII analogue (F8A).
18. The device of claim 17 , wherein a dose of F8 or F8A in the preparation is in a range of 400 IU±10% to 10,000 IU±10%.
19. The device of claim 17 , wherein a dose of F8 or F8A in the preparation is in a range of 0.01±10% mg to 3 mg±10%.
20. The device of claim 1 , wherein the clotting factor comprises Factor VII (F7) or a Factor VII analogue (F7A).
21. The device of claim 20 , wherein a dose of F7 or F7A in the preparation is in a range of 0.03 mg±10% to 3 mg±10%.
22. The device of claim 20 , wherein a dose of F7 or F7A in the preparation is in a range of 1.5 mg±10% to 10 mg±10%.
23. The device of claim 20 , wherein a dose of F7 or F7A in the preparation is in a range of 400 IU±10% to 10,000 IU±10%.
24. The device of claim 1 , wherein the clotting factor comprises Factor IX (F9) or a Factor IX analogue (F9A).
25. The device of claim 24 , wherein a dose of F9 or F9A in the preparation is in a range of 0.03±10% mg to 3 mg±10%.
26. The device of claim 24 , wherein a dose of F9 or F9A in the preparation is in a range of 400 IU±10% to 10,000 IU±10%.
27. The device of claim 24 , wherein a dose of F9 or F9A in the preparation is in a range of 7 mg±10% to 10.6 mg±10%.
28. The device of claim 1 , wherein the clotting factor comprises Factor X (F10) or a Factor X analogue (F10A).
29. The device of claim 28 , wherein a dose of F10 or F10A in the preparation is in a range of 0.03 mg±10% to 3 mg±10%.
30. The device of claim 28 , wherein a dose of F10 or F10A in the preparation is in a range of 20 mg±10% to 33 mg±10%.
31. The device of claim 28 , wherein a dose of F10 or F10A in the preparation is in a range of 400 IU±10% to 10,000 IU±10%.